tag:blogger.com,1999:blog-5906888241303807622024-03-11T21:52:05.500-07:00Sam and Larsmildredhttp://www.blogger.com/profile/02034924909970073272noreply@blogger.comBlogger205125tag:blogger.com,1999:blog-590688824130380762.post-60703525069369604542019-09-20T14:04:00.000-07:002019-09-20T14:04:05.916-07:00At the Top of Sam's Wish List<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7PFETzKBdC8T8dUXrP_i5-9DVIalXQ1uG5RUgHTAI7B_rWyLvcoSaiTwqb5SfY_7B1NUV0gvW3Pn8Ls4YekiRAJnDXqq6z16xfkm98Mix7mKHyaet6sn7YJ1kV1GkC0EsUEMVOVQngoDa/s1600/baby_cage1.jpg" onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}"><img alt="" border="0" id="BLOGGER_PHOTO_ID_5539262857910009778" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7PFETzKBdC8T8dUXrP_i5-9DVIalXQ1uG5RUgHTAI7B_rWyLvcoSaiTwqb5SfY_7B1NUV0gvW3Pn8Ls4YekiRAJnDXqq6z16xfkm98Mix7mKHyaet6sn7YJ1kV1GkC0EsUEMVOVQngoDa/s320/baby_cage1.jpg" style="cursor: hand; cursor: pointer; display: block; height: 160px; margin: 0px auto 10px; text-align: center; width: 320px;" /></a><br />
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I find this humorously (it's a word and it works here) disturbing. However, I'm quite certain that Sam would really love something like this and could possibly sit in one for hours while observing people pass by. He's always pointing at the front door so we'll take him outside. We usually do. He's not getting this cage though. Sorry Sam.Unknownnoreply@blogger.com7tag:blogger.com,1999:blog-590688824130380762.post-23320354539449361072019-09-20T14:02:00.000-07:002019-09-20T14:02:37.110-07:00<div style="text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjhHnUxBfBwSfkAvq0y8hRp9_2T-Lc0OmLGBLzzVgHMayz4jJdDq7RDHAGvPHdUq62nuWvJ_rip13p4t8DyeLCTqHOUppd4iAXqI7zbujQ7SwrNkSWZ5fqgYH8k2ZihQDB7cukM8N7x2B7Z/s1600/Sambo" onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}"><img alt="" border="0" id="BLOGGER_PHOTO_ID_5580052063581727458" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjhHnUxBfBwSfkAvq0y8hRp9_2T-Lc0OmLGBLzzVgHMayz4jJdDq7RDHAGvPHdUq62nuWvJ_rip13p4t8DyeLCTqHOUppd4iAXqI7zbujQ7SwrNkSWZ5fqgYH8k2ZihQDB7cukM8N7x2B7Z/s400/Sambo" style="cursor: pointer; display: block; height: 361px; margin: 0px auto 10px; text-align: center; width: 400px;" /></a><br />
We can't wait to be outside all day long.</div>
mildredhttp://www.blogger.com/profile/02034924909970073272noreply@blogger.com3tag:blogger.com,1999:blog-590688824130380762.post-57213508115357278122019-04-08T19:05:00.005-07:002019-04-08T20:50:46.045-07:00Cystinosis Research Foundation Day of Hope 2019<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvGCvvp0iYcNCSGeumfx0okJgDlGgTqO-BcJEeUJEaA_vzS1VB4DiaxJAnlLYYfDsPz_rJRxgAjGYZdR77VJJ5l1cWND1Awlnz6K-kcFnZZsxeqTsvDTAjPhTLqHWLttzktzCpsatsqh0/s1600/IMG_9036.JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="1600" data-original-width="1200" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvGCvvp0iYcNCSGeumfx0okJgDlGgTqO-BcJEeUJEaA_vzS1VB4DiaxJAnlLYYfDsPz_rJRxgAjGYZdR77VJJ5l1cWND1Awlnz6K-kcFnZZsxeqTsvDTAjPhTLqHWLttzktzCpsatsqh0/s640/IMG_9036.JPG" width="480" /></a></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We just got back from the Day of Hope family conference, and it felt different this year. There was an extra large dose of hope infused into all the activities. I think that hope stemmed from the upcoming stem cell trial for adults with cystinosis, something we've all been waiting and praying for.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We had a record 68 families attend this year, with people from the United States, Canada, Ireland, France, Sweden and Australia. There were many newly diagnosed families, and some other people who attended for their first time. It was so great to meet new people, and to catch up with old friends. Our boys were especially excited to see Henry Sturgis. They are his biggest fans.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We started the conference on Thursday with introductions. This is always a tender part, especially for new families. Everyone told a little bit about themselves and shared a wish, written on a star. For the last several years, my wish has been the same: that Sam and Lars will have happy and healthy lives. This year felt different, and my wish was more concrete. I wished that we would see the first adult with cystinosis start the stem cell transplant trial, and that it would work. Many people shared similar wishes. After introductions we had delicious Mexican food while the children ran wild throughout the hotel. It's the one time a year I eat churros because they are too good to pass up.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Friday morning started bright and early. Nancy Stack, the president of the Cystinosis Research Foundation, gave us an update on all the work the CRF is doing. Since they started in 2003, the CRF has raised over $50 million, funding over 180 grants to over a hundred scientists, resulting in 76 publications. We are funding numerous basic science studies, as well as multiple promising translational research projects.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Nancy's talk, I gave a brief presentation on the basics of cystinosis. The cell's genetic blueprint, DNA, is like instructions for building Lego sets. The Lego blocks are like amino acids. The completed Lego creation is like a protein. If there is an error in the Lego instructions (DNA), then you can't build the protein correctly. This is what happens in cystinosis. There is a mutation in the DNA that explains how to build the cystinosin protein. If you want to cure cystinosis, you have to find a way to correct the instructions in every cell of the body.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next, we heard from Dr. Julian Midgley, from
Alberta Children’s Hospital in Calgary, Canada.</span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">
</span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">He talked about the important and complex process of transitioning from
pediatric to adult care.</span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"> </span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">As a pediatric
nephrologist, he primarily cares for pediatric patients, but he has continued
to follow many adults with cystinosis as well.</span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"> He recommended starting early and planning ahead. Don't wait until the child's 18th birthday. </span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">He noted that when cystinosis patients are young they get excellent care
because their parents control everything.</span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">
</span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">As they grow older and become adolescents and teenagers, there is often
some rebellion and adherence to medications may decline. As people age and mature, they usually improve their adherence, but never back to the same level as when their parents were in control. He talked about how oftentimes parents need to remain involved in their child's care even after transitioning to adult providers. It will be different for each child and each family, and should be tailored to the patient's needs. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Ranjan Dohil from UCSD talked about the GI effects of cystinosis and cysteamine therapy. He believes that cystine accumulation likely affects the muscles of the stomach, which can lead to dysmotility and gastroparesis. He showed his research that cysteamine itself causes increased acid production, which can lead to heartburn and nausea. This is improved with a proton-pump inhibitor like omeprazole, but there may be risks to taking long term PPIs, like low magnesium levels and possibly osteoporosis. He talked about gastrostomy tubes and the importance of changing the size as the child grows. He also talked about the importance of taking Procysbi or Cystagon on an empty stomach. Both of these drugs have impaired absorption when taken with foods that are high in fat and protein. He recommended fasting before for two hours, and then fasting after for at least thirty minutes (although some people may need to fast up to two hours depending on how quickly their stomach empties). He recommended eating foods high in carbohydrates, like fruit and grains, after taking cysteamine, as this does not affect absorption as much (bacon and eggs is not the best for breakfast). He emphasized that everyone will have to do what works for them. Do the best you can with the dietary restrictions, and make sure your white blood cell cystine levels are well-controlled. If you notice significant fluctuations in the white blood cell cystine levels, it may be a sign that your diet is inconsistent. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Grimm from Stanford about chronic kidney disease and anticipating the need for dialysis and kidney transplant. He pointed out that creatinine is a byproduct of muscle, so the more muscle you have, the higher your creatinine will be, and the lower your muscle mass, the lower your creatinine will be. A more accurate way to measure kidney function is a lab called cystatin C. He recommended using the CKiD formula for calculating glomerular filtration rate (GFR) in children <a href="https://www.kidney.org/professionals/kdoqi/gfr_calculatorped" target="_blank">(link here)</a>. For adults, the best way to calculate GFR is the CKD-Epi calculator <a href="https://www.kidney.org/professionals/KDOQI/gfr_calculator" target="_blank">(link here)</a>. Your GFR can be plotted on a graph, and typically declines in a predictable, linear fashion. This allows you to prepare for when you or your child may need dialysis or transplant. He talked about things that make your GFR worsen faster, including obesity, acidosis (low bicarbonate levels), low potassium, and diets high in animal fat and protein. He recommended the DASH diet, which is rich in fruits and vegetables, to delay GFR deterioration. He also recommended strict cysteamine adherence, as this has been shown to delay GFR decline. He emphasized that some cystinosis mutations are worse than others, and some people are just unlucky. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Robert Mak from UCSD talked about his research on inflammation in cystinosis. He is studying the NLRP3 pathway, which is activated in mice with cystinosis and leads to increased inflammation, which is associated with muscle wasting and bone disease. He tested some IL-1 inhibitors that are already available in cystinosis knockout mice, and found that they had improved muscle mass, muscle strength, stronger bones and fewer fractures. He also found, unexpectedly, that their Fanconi syndrome also improved. He plans to test these drugs further in his cystinosis knockout mice and hopes to do a study in humans. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Mak we heard from Dr. Kathleen Rickert, also from UCSD. She is an orthopedic surgeon, and spoke about common leg abnormalities in cystinosis, including bowleggedness (varus deformity) and the more common knock-knees (valgus deformity). All children go through a normal evolution of alignment, starting with bowleggedness when they first walk, which corrects to neutral alignment, but then often overcorrects to knock knees around age 4. This will eventually correct back to neutral alignment by age 8. If you or your child has knock knees after age 8, then you should see an orthopedic surgeon. It can be corrected with growth-modulating surgery. These alignment abnormalities can cause knee pain, difficulty running and gait disturbances. She saw multiple patients in bone clinic last year with Dr. Mak and shared their findings. They found that the most common abnormality was mild valgus and flat feet. Flat feet can exaggerate the appearance of valgus deformity, and can be treated with good inserts and SMO braces. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next, we heard from a new speaker, Dr. Richard Reimer from Stanford, who is an adult neurologist. He has been seeing patients with Dr. Paul Grimm in their cystinosis clinic. Cystinosis muscle disease causes hand weakness and swallowing difficulties. He is working with Dr. Mary Leonard, who did a previous study with Dr. Grimm of bone and muscle characteristics in 39 individuals with cystinosis. They found that people with cystinosis have less lean muscle mass, strength and endurance. He plans to do a study of high intensity interval training (HIIT) to see whether it improves any of those outcomes. He thinks there may be a mitochondrial component to cystinosis muscle disease, and plans to study mitochondrial function in the trial participants with CrCEST imaging. He recommended using a mitochondrial cocktail as a possible treatment for muscle wasting. He recommended a brand called "Mito-Tonic" <a href="https://www.amazon.com/MITO-TONIC-Energy-Drink-Mix-225-Gram/dp/B00EKPJA8O/ref=sr_1_fkmrnull_1?keywords=mito+tonic&qid=1554767493&s=gateway&sr=8-1-fkmrnull" target="_blank">(Amazon link here)</a> which includes coenzyme Q10, levocarnitine and B vitamins.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Marya Bengali and Spencer Goodman, who work in Dr. Cherqui's lab. For the last couple years, they have been collecting photographs of skin from people with cystinosis with a special hand-held microscope called a Vivascope. They found that cystine crystals accumulate in the skin, especially in the papillary dermis region. They found that people who are not compliant with cysteamine therapy have a lot more crystals. This may be a way of monitoring long term compliance. They will use the Vivascope to evaluate participants in the stem cell transplant trial to see if skin crystals are reduced. </span><br />
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next, Dr. Stephanie Cherqui talked to us about the upcoming Phase I/II trial for gene-corrected autologous stem cell transplant. She got approval from the FDA back in December 2018, and is hoping to recruit the first patient in May or June. There will be 6 patients in this phase. Eligible patients must be over 18 years old and have good organ function. They can have a kidney transplant, but must be at least 12 months out from transplantation. Interested candidates will come to San Diego and go through 2-4 days of screening and information. If they decide they want to do it, they will come back for 8-9 days for a full, intensive examination, which will include evaluation of kidneys, eyes, lungs, heart, endocrine glands, muscles, bones and neurologic function and quality of life. If they are deemed healthy enough to participate, they will undergo stem cell harvest. Blood is taken and sent to UCLA. At this point the patient goes back home. At UCLA the stem cells are modified with a lentivirus vector, which takes about 60-90 days. The patient must stop oral cysteamine two weeks before the transplant, and eye drops two months before. The patient then returns to San Diego to get the transplant. </span><br />
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Ted Ball from UCSD talked about the actual transplant process. He is a hematologist/oncologist and has done over 2,000 transplants in his career. Before the transplant, patients will receive busulfan to make room in the bone marrow. It's given every 6 hours over 4 days. Then the patient's corrected stem cells are infused back into the patient. The next two weeks are critical because the patient won't have any white blood cells. All patients will receive prophylactic antibiotics, including ciprofloxacin, fluconazole and acyclovir, since they won't have an immune system to fight off infections. It's very common at day 5 or 6 to have fevers, and if that happens the antibiotics would be broadened. At day 7 they will receive a medication called neupogen that stimulates the bone marrow to release white blood cells. It's common to need blood or platelet transfusions during this period. Usually by day 12 the blood counts return to normal. Common side effects of the chemotherapy include sores in the mouth (mucositis), diarrhea, hair loss (it comes back!) and pneumonitis (lung inflammation) 30-60 days after transplant. Pneumonitis is treated with steroids. Infertility is common, so anyone who wants to have children will need to bank sperm or eggs ahead of time. Very rarely the chemotherapy can lead to hematologic cancer in the future. The mortality rate for an autologous transplant is very low, estimated 1-2%, but is not without risk. It is much safer than an allogeneic transplant, however, which has a 20% mortality rate. After the transplant, patients will be in the hospital for 2-3 weeks. After discharge they will have to stay in San Diego for a couple months, with frequent outpatient follow-up visits. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Sergio Catz from the Scripps Research Institute. He spoke to us about his research on chaperone-mediated autophagy. There is a receptor called LAMP2A that recognizes which proteins need to be degraded in the lysosome, and facilitates the internalization of these proteins. In cystinosis cells, this receptor is not located in the lysosomal membrane, which leads to a build up of proteins outside the lysosome. This is not corrected with cysteamine. He is collaborating with another scientist, Ana Maria Cuervo, who has discovered a compound, QX77 (also called CA77), which corrects this defect, and improves cellular trafficking, autophagy and response to external stress. He is testing this compound in cystinosis knockout mice, and has found decreased cellular </span><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">stress, improved LAMP2A distribution and increased megalin expression. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Catz we heard from Dr. Matthew Wade, an ophthalmologist from UC-Irvine. He talked about how lots of things besides corneal crystals can cause light sensitivity, so patients should be vigilant and get regular eye checks. He emphasized it is particularly important for an ophthalmologist to check the optic discs. Abnormal optic discs can be a sign of increased intracranial pressures, which can cause headaches and blindness. He also talked about benzalkonium chloride (BAK), which is the common preservative found in eye drops. BAK roughs up the surface of the eye to let the drug in, but in the process can cause dry eye, eye pain, light sensitivity and foreign-body sensation. He recommended using preservative-free eye drops if you develop dry eye disease from the cysteamine eye drops.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Morgan Fedorchak of the University of Pittsburgh. She has developed a controlled-release eye drop. It is a thermo-responsive hydrogel that turns from liquid to solid when it touches the eye. The gel is filled with microspheres loaded with cysteamine. She has been manufacturing the eye drops at a cGMP facility, which means it will be much faster to scale up production for a trial. She is doing a rabbit study to test for toxicity and should be finished with that later this year. She is starting her knockout mouse study now and will hopefully finish that in the first part of 2020. After that she can apply to the FDA to do a human trial.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Doris Trauner from UCSD shared the results of her study on sleep apnea in people with cystinosis. She was able to do sleep studies on 19 people, 8 women and 11 men. The majority had sleep apnea (58%). 16 of the 19 people had abnormally low oxygen saturations during the night and most had multiple nocturnal awakenings. While sleep apnea is often thought of as a disease of older, obese people, she found that it was common even in young, thin adults. Sleep apnea is treated with continuous positive airway pressure (CPAP). All adults would benefit from being screened. The study is ongoing and they continue to enroll more adults. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After a full day of science, we were ready for some fresh air and fun. Buses transported everyone to the Back Bay park and beach, where we had a fantastic barbecue feast. I may have started with dessert this year. Lars sampled every flavor of cotton candy. They also had these life-changing Hungarian chimney cake ice cream cones. We spent a lot of the evening talking about the upcoming stem cell trial, excited about the prospect of a cure.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Saturday morning we were back at it with Dr. Grimm. This time he talked about dialysis and transplants. He explained why it's ideal to get a transplant before you even need dialysis. Adults can usually get listed for transplant once their GFR is 20, while kids can get listed for transplant when they have a GFR of 60. Kids get to be on the top of the transplant list, so it's better to get listed before you turn 18 years old. Living donor kidneys are the best, even if it's not as well-matched. There has been a decline in living parent donors because of the rise of obesity, diabetes and hypertension, and there are more single parent families. The average kidney transplant lasts about 15-20 years. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">If you're not able to get a kidney transplant right away, then you may need dialysis. There are two ways to do dialysis: hemodialysis and peritoneal dialysis. Hemodialysis is initially done through a central catheter that goes into the internal jugular vein. It has to be done three times a week for 3-4 hours, although some people are able to get a home unit that can be run every day. Patients who plan to do hemodialysis long term get something called an arteriovenous fistula. This made by a vascular surgeon. Because you need good veins to make a fistula, Dr. Grimm recommended that everyone should avoid blood draws and IVs in the antecubital fossa (where your elbow bends) if possible, and should try the veins of the hands first. If you need a long-term IV for antibiotics, instead of a PICC line you should get a tunneled internal jugular line, because PICC lines can damage the veins of the arm. The other kind of dialysis is peritoneal dialysis. This is done by placing a catheter into the abdominal cavity and filling it with special dialysis fluid. This kind of dialysis can be done at home or even on vacation. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Grimm spoke, we heard from Dr. Benjamin Freedman from University of Washington in Seattle.<span style="background-color: white; color: #222222;"> He and other researchers at the Institute for Stem Cell & Regenerative Medicine at the University of Washington have figured out a way to use viable cells harvested from a patient’s urine to create “mini-organs”. In the laboratory Dr. Freedman can reprogram adult cells into Induced Pluripotent Stem Cells (iPS). These cells are functionally similar to embryonic stem cells. These iPS cells can be reprogrammed into cells which resemble organs in the body, including kidneys. These “kidneys-in-a-dish” can be used to better understand how cystinosis impacts the kidneys as well as test new treatment therapies. Additionally, this technique may one day be used to create new organs or organ grafts from the patient’s own cells. Dr. Freedman has already demonstrated that this process can be used to create kidney cells from patients with polycystic kidney disease (PKD). Dr. Freedman has already cultured cells collected from three patients with cystinosis and with the suitcase full of urine he collected at the conference, we are sure to hear more developments from him in the near future.</span></span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><span style="background-color: white; color: #222222;">Next we heard from Dr. Paul Goodyer about a possible new treatment for people with nonsense mutations. </span><span style="background-color: white; color: #222222;">There are more than 100 different genetic mutations that have been found to cause cystinosis. One type of mutation is called a “nonsense” mutation, which results in the premature termination of protein synthesis. </span><span style="background-color: white; color: #222222;">Dr. Goodyer’s research has shown that approximately 20% of patients with cystinosis in North America have a nonsense mutation from at least one parent. It has been observed that aminoglycoside antibiotics have a peculiar side-effect of allowing the body’s natural genetic mechanisms to ignore or “read-through” nonsense mutations and enable the creation of a complete and functional protein. Dr. Goodyer is working with a pharmaceutical company who has modified the antibiotic gentamicin to remove its antibiotic properties as well as some of its known toxicities, all while maintaining the compound’s ability to allow read-through and complete protein creation. Dr. Goodyer has already demonstrated the compound’s ability to work in mice with cystinosis as well as human cells in the laboratory. Dr. Goodyer expects a human clinical trial to be conducted in Canada starting within the year.</span></span><br />
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<span style="background-color: white; color: #222222;"><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After the last science talk we had breakout sessions for different age groups, which allowed people in different phases of their cystinosis journey to connect with other people who were going through similar experiences. In the 0-8 group we talked a lot about eating, medications and self-care for parents. The 8-17 group talked a lot about school, friends and medication compliance. The adults with cystinosis and their partners met with Dr. Grimm and Dr. Dohil to discuss issues important to them. Parents of adults with cystinosis also got together to talk about the challenges unique to them. </span></span><br />
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<span style="background-color: white; color: #222222;"><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After the breakout sessions, we had a question and answer panel with all the researchers and physicians. Following that we did a panel with our adults with cystinosis. There were twelve adults on the panel this year. They talked about the amazing things they are doing in their lives. On the panel we had a dental assistant, two pre-school teachers, an oil field worker, a high school teacher, a consumer health company consultant, a clothing store owner, a landscape designer, non-profit employee who works with foster children, a certified welder and a police officer (sorry if I missed anyone). They talked about not limiting your children and letting them pursue the activities and dreams that they want. They talked about the importance of gradually transferring responsibility and not treating them as the sick kid. They talked about how much better life was after getting their kidney transplants. They talked about the hope they have for the future. It was a pretty inspiring group of people. </span></span><br />
<span style="background-color: white; color: #222222;"><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span></span>
<span style="background-color: white; color: #222222;"><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Saturday night we got together again for the Natalie's Wish event. Dr. Stephanie Cherqui was the guest of honor, and gave an emotional speech about her work and the gratitude she has to all the cystinosis families who support and believe in her. She said families tell her thank you all the time, and she frequently tells them, "Well, we don't even know if it works yet." The families reply, "Thank you for even trying to find a cure." Dr. Cherqui was presented with a special gift from the foundation (including a trip to Hawaii!) by Tina Flerchinger and other children with cystinosis. We had over twenty families present checks to the CRF, and altogether we raised an incredible $4.1 million in one night. All of that money will go directly to research to find a cure and better therapies for cystinosis. </span></span><br />
<span style="background-color: white; color: #222222;"><span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span></span>
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We left the conference so full
of hope, and so grateful for everything the Stack family and the CRF are doing
to improve the lives of those affected by cystinosis. I look forward to
seeing everybody again next year. And if you’ve never been to the
conference and want to come, please reach out to the CRF. We’d love
to see you there next year!</span></div>
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<br />stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-39713721143354047832018-04-26T19:23:00.000-07:002018-05-03T21:21:33.932-07:00CRF Day of Hope 2018<!--[if gte mso 9]><xml>
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<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitcEXspynj6kLtwj0LnJZwa2Lxm4xjC63Z9LhSLT3E0rPTda-zaQ2d7i3BDQEd6QxxiHC7CQR5_TqZCAYI0rVLVk0PJ_4N333hDr3-IO-kOfJoOvSjyCDvNbKnJyHDYkpOK1yzOa7hTco/s1600/day+of+hope+2018.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="1170" data-original-width="1170" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitcEXspynj6kLtwj0LnJZwa2Lxm4xjC63Z9LhSLT3E0rPTda-zaQ2d7i3BDQEd6QxxiHC7CQR5_TqZCAYI0rVLVk0PJ_4N333hDr3-IO-kOfJoOvSjyCDvNbKnJyHDYkpOK1yzOa7hTco/s640/day+of+hope+2018.png" width="640" /></a></div>
<span style="font-size: large;"><br /></span>
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">This year’s Day of Hope Family Conference was an enormous
success.<span style="mso-spacerun: yes;"> </span>We had 61 families from all
over the world attend this year.<span style="mso-spacerun: yes;"> </span>There
were families from Australia, Sweden, Norway, Ireland and Canada.<span style="mso-spacerun: yes;"> </span>We were excited to welcome 16 new families,
ranging from newly diagnosed infants to adults.<span style="mso-spacerun: yes;">
</span><o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">On Thursday night we all got together for
introductions.<span style="mso-spacerun: yes;"> </span>We all shared a little
bit about ourselves, as well as our wishes and hopes. <span style="mso-spacerun: yes;"> </span>Everyone expressed hope for a cure for
cystinosis, but also that no matter what happens, that those affected by
cystinosis will not feel limited or defined by their disease, and that
everybody would lead happy, healthy lives.<span style="mso-spacerun: yes;">
</span>After introductions we had delicious Mexican food, something I’ve come
to look forward to every year.<span style="mso-spacerun: yes;"> </span>Our boys
chowed down on chicken quesadillas while their friend, Henry Sturgis, ate his
weight in chocolate-covered churros.<span style="mso-spacerun: yes;"> </span>It
was the perfect venue for catching up and getting to know the new families. <o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">On Friday morning we got started bright and early.<span style="mso-spacerun: yes;"> </span>Nancy Stack updated us on the amazing
progress of the Cystinosis Research Foundation.<span style="mso-spacerun: yes;">
</span>Altogether the foundation has raised over $40 million for cystinosis
research since its inception in 2003, funding 164 studies in 12 different
countries.<span style="mso-spacerun: yes;"> </span>It’s pretty remarkable that
such a vibrant research community has sprung up around such a rare
disease.<span style="mso-spacerun: yes;"> </span>After Nancy spoke it was my
privilege to go over the basics of cystinosis at the cellular and organ
levels.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Paul Grimm from Stanford spoke about the genetics of
cystinosis.<span style="mso-spacerun: yes;"> </span>There are over 100 different
mutations identified in cystinosis.<span style="mso-spacerun: yes;"> </span>The
most common is the 57kb mutation, which affects 50-75% of people of Northern
European descent.<span style="mso-spacerun: yes;"> </span>What mutations you
have determines a lot about how cystinosis manifests.<span style="mso-spacerun: yes;"> </span>Some people have very severe Fanconi
syndrome, while others have very severe corneal disease.<span style="mso-spacerun: yes;"> </span>Some people don’t sweat or tolerate heat very
well.<span style="mso-spacerun: yes;"> </span>If you have the 57kb mutation, you
also have a mutation in the receptor that detects heat from hot chili peppers.<span style="mso-spacerun: yes;"> </span>This endows you with the ability to eat very
spicy foods.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Grimm also talked about the upcoming Phase 2 trial for a
drug called ELX-02 that may allow people with nonsense mutations to make a
functional cystinosin protein.<span style="mso-spacerun: yes;"> </span>It will
be administered as an injection, given 2-3 times a week, and may eliminate the
need for cysteamine therapy.<span style="mso-spacerun: yes;"> </span>If you have
the nonsense mutation, you should check it out!<span style="mso-spacerun: yes;">
</span>Dr. Grimm also pointed out that most people in the United States don’t
get genetic testing because it’s usually not covered by insurance.<span style="mso-spacerun: yes;"> </span>If you would like to get your genetics done,
there are companies like <a href="http://www.invitae.com/">www.invitae.com</a>
that charge about $200 to run your mutation. <span style="mso-spacerun: yes;"> </span>They will even work with your insurance
company to try to get it covered. <o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Ranjan Dohil from UC San Diego spoke about the
gastrointestinal effects of cystinosis.<span style="mso-spacerun: yes;">
</span>He showed us his research on how cysteamine itself causes many of the GI
symptoms, including a surge of stomach acid production, nausea, and delayed
gastric emptying.<span style="mso-spacerun: yes;"> </span>He also talked about
the research that led to delayed-release cysteamine, or Procysbi.<span style="mso-spacerun: yes;"> </span>He emphasized that fatty foods significantly
decrease absorption of Procysbi, which is one of the reasons it’s important to
fast before and after.<span style="mso-spacerun: yes;"> </span>Although the
package insert says to fast two hours before and thirty minutes after, he said
everyone needs to adjust to their own schedule, lifestyle and needs.<span style="mso-spacerun: yes;"> </span>Some people may need to wait longer than 30
minutes before eating, if they have delayed gastric emptying.<span style="mso-spacerun: yes;"> </span>Everyone’s dose will have to be titrated
individually. <o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Robert Mak from UC San Diego shared his research on
muscle disease in cystinosis.<span style="mso-spacerun: yes;"> </span>He has
discovered an inflammation pathway that appears to be implicated in muscle
wasting and bone disease in cystinosis.<span style="mso-spacerun: yes;">
</span>He has found two drugs that block this pathway. In cystinosis knockout mice,
these drugs improve bone and muscle mass dramatically.<span style="mso-spacerun: yes;"> </span>He is hopeful to move forward on a clinical
trial in humans.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Kathleen Rickert was a welcome new face this year.<span style="mso-spacerun: yes;"> </span>She is an orthopedic surgeon from UC San
Diego.<span style="mso-spacerun: yes;"> </span>Although she has not previously
seen patients with cystinosis, she has started a collaborative clinic with Dr.
Mak at UCSD to see children and adults with bone deformities.<span style="mso-spacerun: yes;"> </span>She reviewed the common bone complications in
cystinosis, including bowleggedness and knock-knees, and the different medical
and surgical ways to manage them.<span style="mso-spacerun: yes;"> </span>She
recommended getting X-rays periodically to monitor progression of the
deformities.<span style="mso-spacerun: yes;"> </span>I look forward to hearing
again from her in the future.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Rachel Duong from Massachusetts General Hospital shared
results from a study by Dr. Florian Eichler on muscle complications in adults
with cystinosis.<span style="mso-spacerun: yes;"> </span>They used several
validated surveys to measure symptoms of muscle weakness and trouble
swallowing, and then various tools including grip strength, peak air flow and
video swallow evaluations to evaluate the extent of muscle disease.<span style="mso-spacerun: yes;"> </span>They found that 14 out of 20 patients
reported symptoms of weakness, while 17 patient demonstrated weakness on
exam.<span style="mso-spacerun: yes;"> </span>They also found that while 12 out
of 20 expressed having trouble swallowing, only 6 actually showed evidence of
abnormal swallowing on video fluoroscopy.<span style="mso-spacerun: yes;">
</span>They will bring these 20 people back in a year to repeat the tests to
measure progression, and train them on some potential exercises they can do to
improve muscle function.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Julian Midgley, from Alberta Children’s Hospital in
Calgary, Canada, spoke to us about the important and complex process of transitioning
from pediatric to adult care.<span style="mso-spacerun: yes;"> </span>In his
unique practice, he is actually allowed to see both children and adults with
cystinosis.<span style="mso-spacerun: yes;"> </span>He recommended starting
early and planning ahead; don’t till the child’s 18<sup>th</sup> birthday.<span style="mso-spacerun: yes;"> </span>It will be different for each child and each
family, and should be tailored to the patient’s needs.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Morgan Fedorchak from University of Pittsburgh spoke to
us on a new controlled-release eye drop she is developing.<span style="mso-spacerun: yes;"> </span>She uses a thermo-responsive hydrogel that
turns from liquid to solid when it touches the eye.<span style="mso-spacerun: yes;"> </span>The gel is filled with microspheres loaded
with cysteamine.<span style="mso-spacerun: yes;"> </span>She has found that
cysteamine is a much harder drug to deal with than other drugs she has used,
which has required a lot of additional testing and trouble-shooting.<span style="mso-spacerun: yes;"> </span>Her initial testing has found that the drug
is detectable in rabbit eyes after 24 hours, so hopefully it can be given once
a day. Next she plans to test them in cystinosis knockout mice. <o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Sergio Catz from Scripps Research Institute spoke to us about
his research on chaperone-mediated autophagy.<span style="mso-spacerun: yes;">
</span>There is a receptor called LAMP2A that recognizes which proteins need to
be degraded in the lysosome, and facilitates the internalization of these
proteins.<span style="mso-spacerun: yes;"> </span>In cystinosis cells, this
receptor is not located in the lysosomal membrane, which leads to a build up of
proteins outside the lysosome.<span style="mso-spacerun: yes;"> </span>This is
not corrected with cysteamine.<span style="mso-spacerun: yes;"> </span>He is
collaborating with another scientist, Ana Maria Cuervo, who has discovered a
compound, QX77 (also called CA77), which corrects this defect, and improves
cellular trafficking, autophagy and response to external stress.<span style="mso-spacerun: yes;"> </span>He is testing this compound in cystinosis
knockout mice, and looking at the kidneys and eyes.<span style="mso-spacerun: yes;"> </span>He has also discovered that there are high
levels of inflammatory proteins from neutrophils (white blood cells that fight
infection) in the serum of cystinosis knockout mice.<span style="mso-spacerun: yes;"> </span>He has found a compound that blocks secretion
of these proteins in cells and he plans to test this compound in cystinosis
knockout mice next.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">After Dr. Catz, we heard from Dr. Stephanie Cherqui on the
upcoming Phase 1-2 clinical trial for autologous hematopoietic stem cell
transplant.<span style="mso-spacerun: yes;"> </span>She is hoping to submit the
IND application to the FDA this summer, and recruit the first patients this
year.<span style="mso-spacerun: yes;"> </span>Eligible patients must be over 18
years old and have good organ function.<span style="mso-spacerun: yes;">
</span>They can have a kidney transplant, but must be at least 12 months out
from transplantation.<span style="mso-spacerun: yes;"> </span>Interested candidates
will come to San Diego and go through 2-4 days of screening and
information.<span style="mso-spacerun: yes;"> </span>They do not have to commit
at that point.<span style="mso-spacerun: yes;"> </span>If they decide they want
to do it, they will come back for 8-9 days for a full, intensive examination,
which will include evaluation of kidneys, eyes, lungs, heart, endocrine glands,
muscles, bones and neurologic function and quality of life.<span style="mso-spacerun: yes;"> </span>If they are deemed healthy enough to
participate, they will undergo stem cell harvest.<span style="mso-spacerun: yes;"> </span>Blood is taken and sent to UCLA.<span style="mso-spacerun: yes;"> </span>At this point the patient goes back
home.<span style="mso-spacerun: yes;"> </span>At UCLA the stem cells are
modified with a lentivirus vector, which takes about 60-90 days.<span style="mso-spacerun: yes;"> </span>Once this process is complete, the patient
returns to San Diego to get the transplant.<span style="mso-spacerun: yes;">
</span>This consist of single agent chemotherapy (busulfan) to make room in the
bone marrow.<span style="mso-spacerun: yes;"> </span>Then the modified stem
cells are infused back into the patient.<span style="mso-spacerun: yes;">
</span>The following month is the riskiest part, as the chemotherapy wipes out
your immune system and makes you susceptible to infections.<span style="mso-spacerun: yes;"> </span>The patient will have to remain in the
hospital for one month until the bone marrow recovers.<span style="mso-spacerun: yes;"> </span>After that they will remain in San Diego for
two additional months, with weekly check ups.<span style="mso-spacerun: yes;">
</span>Then they can go home, but will return every 6 months for 2 years to be
evaluated.<span style="mso-spacerun: yes;"> </span>If things go well for the
first four patients, then the hope would be to do it in adolescents, over 14
years old.<span style="mso-spacerun: yes;"> </span>I’m very hopeful the trial
can start this year.<span style="mso-spacerun: yes;"> </span>Cross your fingers!<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal">
<span style="font-size: large;">Dr. Bruce Barshop spoke about the new granulocyte cystine
test.<span style="mso-spacerun: yes;"> </span>He showed data demonstrating that
overall the newer test has much less variability than the mixed leukocyte
test.<span style="mso-spacerun: yes;"> </span>The goal for the granulocyte
cystine test is less than 1.9.<span style="mso-spacerun: yes;"> </span>The goal
for the mixed leukocyte test is less than 1, although that number is apparently
a little arbitrary and is based on upper limit of normal for carriers.<span style="mso-spacerun: yes;"> </span>He unveiled a new shipping kit that will be
available soon through Horizon, which will hopefully make the packaging and
shipping process much easier.<span style="mso-spacerun: yes;"> </span>If you’d
like a kit, contact your Horizon representative. <o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: large;"><br /></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="font-size: large;"><span style="font-family: "calibri"; mso-ascii-theme-font: minor-latin; mso-hansi-theme-font: minor-latin;">Next we
heard from Dr. Patrice Rioux and Dr. Vince Stanton from Massachusetts.<span style="mso-spacerun: yes;"> </span>They have formed a company, Thiogenesis
Therapeutics, and are working on developing a better form of cysteamine.<span style="mso-spacerun: yes;"> </span></span><span style="color: black; font-family: "calibri"; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: Arial; mso-hansi-theme-font: minor-latin;">They modified cysteamine by adding a molecule to form a new
compound. This compound is metabolized in the gut, where some cysteamine
is absorbed, but some is left in the GI tract, where it continues to be
metabolized and absorbed further downstream. This results in a much lower
peak concentration (which will reduce the side effects of odor and nausea) and
a more sustained blood level of cysteamine.<span style="mso-spacerun: yes;">
</span>They found that a large reservoir also ended up in the colon of mice,
where it continued to be absorbed. This may result in a medication that
could be taken once or twice a day, with better efficacy and fewer side effects
than Cystagon or Procysbi.<span style="mso-spacerun: yes;"> </span>They are
hoping to move forward with a study, possibly in Australia, to test toxicity in
humans. <o:p></o:p></span></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="font-size: large;"><br /></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="color: black; font-family: "calibri"; font-size: large; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: Arial; mso-hansi-theme-font: minor-latin;">After a long day of talks we were ready to get outside and
have dinner.<span style="mso-spacerun: yes;"> </span>The CRF arranged for buses
to transport us to the Back Bay park and beach, where we enjoyed a fabulous
barbecue feast.<span style="mso-spacerun: yes;"> </span>My kids were super
excited for the return of the light up cotton candy wands.<span style="mso-spacerun: yes;"> </span>After gorging themselves on macaroni and cheese
and brisket, they ran down to the beach to start a lightsaber battle.<span style="mso-spacerun: yes;"> </span>I had to sample every dessert, which included
fresh donuts and made-to-order ice cream cookie sandwiches.<span style="mso-spacerun: yes;"> </span>I think I gained 10 pounds.<span style="mso-spacerun: yes;"> </span>It was a beautiful setting and a great night
to relax.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="font-size: large;"><br /></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="color: black; font-family: "calibri"; font-size: large; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: Arial; mso-hansi-theme-font: minor-latin;">On Saturday we heard first from Dr. Mary Leonard, from
Stanford.<span style="mso-spacerun: yes;"> </span>She and Dr. Grimm did a study
looking at bone health in children and adults with cystinosis.<span style="mso-spacerun: yes;"> </span>They did a number of tests, including
strength testing, DEXA and high resolution peripheral quantitative computed
tomography to analyze the muscles and bones.<span style="mso-spacerun: yes;">
</span>They found that kids with cystinosis have 32% lower leg strength than
healthy controls, and adults have 35% lower strength.<span style="mso-spacerun: yes;"> </span>Muscle force was 25% lower in kids with
cystinosis, and 13% lower in adults.<span style="mso-spacerun: yes;"> </span>The
cortical bone was thinner and had lower surface area, and had a 19% lower failure
load.<span style="mso-spacerun: yes;"> </span>Amount and thickness of spongy
bone was lower as well.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="font-size: large;"><br /></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="color: black; font-family: "calibri"; font-size: large; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: Arial; mso-hansi-theme-font: minor-latin;">Next Dr. Paul Grimm spoke again, this time about juggling
the many aspects of cystinosis care, especially in younger children.<span style="mso-spacerun: yes;"> </span>He talked about the importance of regular
dosing of supplements for Fanconi syndrome, especially phosphorus, potassium
and bicarbonate/citrate. <span style="mso-spacerun: yes;"> </span>He also talked
about important medication interactions.<span style="mso-spacerun: yes;">
</span>Calcium should not be given with phosphorus (neither will get
absorbed).<span style="mso-spacerun: yes;"> </span>Procysbi should not be given
with bicarbonate (the high pH will dissolve the beads prematurely).<span style="mso-spacerun: yes;"> </span>Citrate and bicarbonate should not be
combined (it causes a fizzy chemical reaction, which is a good recipe for
burping).<span style="mso-spacerun: yes;"> </span>He talked about indomethacin,
and using it to reduce fluid and electrolyte losses.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="font-size: large;"><br /></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="color: black; font-family: "calibri"; font-size: large; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: Arial; mso-hansi-theme-font: minor-latin;">The next talk was from Dr. Doris Trauner from UCSD.<span style="mso-spacerun: yes;"> </span>I missed her talk, but she reported her
results on a study of adults with cystinosis for sleep apnea and its possible
connection to memory troubles.<span style="mso-spacerun: yes;"> </span>The
majority of adults tested had sleep apnea, half of which had moderate to severe
sleep apnea.<span style="mso-spacerun: yes;"> </span>This was previously
undiagnosed, which suggests that all adults would benefit from being
screened.<span style="mso-spacerun: yes;"> </span>She is still actively
recruiting patients to undergo overnight sleep studies.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="font-size: large;"><br /></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="color: black; font-family: "calibri"; font-size: large; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: Arial; mso-hansi-theme-font: minor-latin;">While Dr. Trauner gave her talk, Dr. Grimm and Dr. Dohil met
with the adults with cystinosis, and I met with the kids ages 11-14.<span style="mso-spacerun: yes;"> </span>For me it was very eye-opening to hear these
young kids talk openly about their challenges.<span style="mso-spacerun: yes;">
</span>It was also cool to see how much they support each other.<span style="mso-spacerun: yes;"> </span>I hope we can have another session next year.
<o:p></o:p></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="font-size: large;"><br /></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="color: black; font-family: "calibri"; font-size: large; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: Arial; mso-hansi-theme-font: minor-latin;">After the last session we had a question and answer panel
with all our researchers and physicians.<span style="mso-spacerun: yes;">
</span>Following that we had a question and answer panel with our adults with
cystinosis.<span style="mso-spacerun: yes;"> </span>They talked about how they
had overcome many of the challenges of cystinosis and living with a chronic
illness.<span style="mso-spacerun: yes;"> </span>They talked about working,
staying active, being compliant with medications, and how to live a full
life.<span style="mso-spacerun: yes;"> </span>Every year I hear from them I am
inspired by their courage and hope.<o:p></o:p></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="font-size: large;"><br /></span></div>
<div style="margin-bottom: .0001pt; margin: 0in;">
<span style="color: black; font-family: "calibri"; font-size: large; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: Arial; mso-hansi-theme-font: minor-latin;">Saturday night we reconvened for the Natalie’s Wish
gala.<span style="mso-spacerun: yes;"> </span>We enjoyed the great entertainment
and gourmet dinner (including a unicorn cheesecake with edible glitter!), and
were blown away by the generosity of the attendees.<span style="mso-spacerun: yes;"> </span>We had 25 families present checks to the CRF
this year, raising $668,000.<span style="mso-spacerun: yes;"> </span>Altogether
the CRF raised an incredible $3.5 million.<span style="mso-spacerun: yes;">
</span>The best part is that all that money will go directly to research.<span style="mso-spacerun: yes;"> </span>We left the conference so full of hope, and
so grateful for everything the Stack family and the CRF are doing to improve
the lives of those with cystinosis.<span style="mso-spacerun: yes;"> </span>I
look forward to seeing everybody again next year.<span style="mso-spacerun: yes;"> </span>And if you’ve never been to the conference
and want to come, please reach out to the CRF.<span style="mso-spacerun: yes;">
</span>We’d love to see you there next year!<o:p></o:p></span></div>
<!--EndFragment--><br />stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com0tag:blogger.com,1999:blog-590688824130380762.post-85008205691486006332017-09-06T19:56:00.001-07:002017-09-07T17:07:41.251-07:00Thank you<div class="separator" style="clear: both; text-align: center;">
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Some amazing businesses have generously donated to our silent auction. We are incredibly grateful for their support. Every dollar raised will go to medical research to help find a cure for cystinosis. </div>
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<a href="https://www.instagram.com/missywallaceart/" target="_blank"><br /></a></div>
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<a href="https://www.instagram.com/missywallaceart/" target="_blank">V</a>isit Instagram <a href="https://www.instagram.com/samshopeforacure/" target="_blank">@samshopeforacure</a> for details and to bid on Sept. 8th from 9am - Sept. 9 at 9pm.</div>
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<a href="https://www.instagram.com/missywallaceart/" target="_blank">Missy Wallace Art</a> - several butterfly prints</div>
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<a href="https://www.instagram.com/copperfoxlettering/" target="_blank">Copper Fox Lettering</a> - hand lettered quotes</div>
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<a href="https://www.facebook.com/BanburyCrossDonuts/" target="_blank">Banbury Cross</a> - cake</div>
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<a href="http://acburger.com/" target="_blank">Arctic Circle</a> - $50 gift card</div>
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<a href="http://www.thedodorestaurant.com/" target="_blank">The Dodo Restaurant</a> - 2 $20 gift cards</div>
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<a href="https://www.boondocks.com/" target="_blank">Boondock's</a> - 2 adult day passes</div>
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<a href="http://porcupinepub.com/" target="_blank">Porcupine Pub & Grille</a> - 2 $20 gift cards</div>
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<a href="https://www.riograndecafeslc.com/" target="_blank">Rio Grande Cafe</a> - 2 $20 gift cards</div>
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<a href="http://www.cactusandtropicals.com/#about-cactus-and-tropicals" target="_blank">Cactus & Tropicals</a> - $50 gift card</div>
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<a href="https://www.instagram.com/p/BYbqqNKgq_Z/?taken-by=samshopeforacure" target="_blank">Stephanie Ransom</a> - 4 pillow cases</div>
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Maryn Tan - family photoshoot</div>
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Kim Holmes- dental basket</div>
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mildredhttp://www.blogger.com/profile/02034924909970073272noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-11639463248984682342017-08-24T15:36:00.001-07:002017-08-24T15:36:11.874-07:00<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhne3Rg45y7QALvjRyCaW7gL4tWwbzO7-aC5VPslBgjZm7cV6YvEB1KZswze2xmBVTF1FZu3WNlIsCe-RmUCDwHKTpRP2aCXxd8kQ1n5gHCnGxba9ZZkhqM-QLSQxfgkQbQV1jh87thn_a4/s1600/SilentAuctionAnnouncement.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="1600" data-original-width="1537" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhne3Rg45y7QALvjRyCaW7gL4tWwbzO7-aC5VPslBgjZm7cV6YvEB1KZswze2xmBVTF1FZu3WNlIsCe-RmUCDwHKTpRP2aCXxd8kQ1n5gHCnGxba9ZZkhqM-QLSQxfgkQbQV1jh87thn_a4/s640/SilentAuctionAnnouncement.jpg" width="614" /></a></div>
<div style="text-align: center;">
<span style="font-family: Arial, Helvetica, sans-serif;">We will no longer be holding a 5k at Draper Park on September 9th. The good news though is that the silent auction will continue! Follow @samshopeforacure to bid. </span></div>
mildredhttp://www.blogger.com/profile/02034924909970073272noreply@blogger.com0tag:blogger.com,1999:blog-590688824130380762.post-18154611484867732012017-05-04T20:35:00.000-07:002017-08-21T16:55:18.172-07:00Medications of Cystinosis<div class="MsoNormal">
<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;">When our older son Samuel was
first diagnosed with cystinosis, we were overwhelmed by the many new
medications that he was prescribed. Here
is a cheat sheet with some basic facts about many of the medications that you
or your child may be prescribed for cystinosis.
I did not include transplant medications. As always, if you have concerns or questions about medications prescribed to you, talk to your doctor or your pharmacist.<o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Cysteamine</b>:
This is the game-changing drug that was discovered in 1976 and approved by the
FDA in 1994, that slows disease progression.<span style="mso-spacerun: yes;">
</span>Cysteamine enters every cell of the body and binds to cystine molecules
so that they can get out of the lysosome.<span style="mso-spacerun: yes;">
</span>Cysteamine comes in two varieties, Cystagon and Procysbi.<span style="mso-spacerun: yes;"> </span>Cystagon was the original form of the drug
and must be taken every 6 hours to be effective.<span style="mso-spacerun: yes;"> </span>Its common side effects include nausea,
vomiting, abdominal pain and a sulfur smell.<span style="mso-spacerun: yes;">
</span>Its absorption is decreased if taken with protein and fatty foods. <o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;">Procysbi was developed with
funding from the Cystinosis Research Foundation and was approved by the FDA in
2013.<span style="mso-spacerun: yes;"> </span>It contains the same active drug
as Cystagon, but it is encapsulated in acid-resistant beads that do not
dissolve until they arrive in the small intestine, where the pH is more
alkaline.<span style="mso-spacerun: yes;"> </span>This prevents the drug from
being rapidly absorbed in the stomach.<span style="mso-spacerun: yes;">
</span>The delayed absorption makes it possible to take every 12 hours.<span style="mso-spacerun: yes;"> </span>Bypassing the stomach also tends to improve
some of the side effects for some patients, including dyspepsia and
nausea.<span style="mso-spacerun: yes;"> </span>I’ve found that the smell is
still there regardless of which drug you take, but some patients find one is
better than the other.<span style="mso-spacerun: yes;"> </span>The most
important thing with Procysbi is that its absorption is affected by food, so
you should take it on an empty stomach.<span style="mso-spacerun: yes;">
</span>The package insert says to not eat for 2 hours before taking it, and to wait
an additional thirty minutes before eating again.<span style="mso-spacerun: yes;"> </span>You can take it with an acidic food like orange
juice because the beads are resistant to acid.<span style="mso-spacerun: yes;">
</span>You should not take the pills with alkaline foods like milk because the
beads will dissolve prematurely and the drug will not have delayed absorption.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Cysteamine eye drops</b>:<span style="mso-spacerun: yes;"> </span>These drops contain the same
drug as the pills, but since the cornea does not have blood vessels, the oral
version of the drug does not treat corneal crystals.<span style="mso-spacerun: yes;"> </span>The drops should be administered every hour
that the patient is awake to be most effective, but few patients are able to
achieve this frequency.<span style="mso-spacerun: yes;"> </span>Side effects
include eye irritation, eye pain, and headaches.<span style="mso-spacerun: yes;"> </span>Many people have reactions to the
preservative in the drops, benzalkonium chloride.<span style="mso-spacerun: yes;"> </span>It is currently the only approved therapy in
the United States for corneal cystinosis.<span style="mso-spacerun: yes;">
</span>Other countries have eye gels, and some pharmacies will compound eye
drops.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Potassium</b>: People
with cystinosis lose many electrolytes, including potassium, in their urine
because of Fanconi syndrome.<span style="mso-spacerun: yes;"> </span>Low
potassium (hypokalemia) causes muscle weakness, muscle cramps and in severe
cases can lead to cardiac arrhythmias.<span style="mso-spacerun: yes;"> </span>Hypokalemia
is made worse by vomiting and diarrhea.<span style="mso-spacerun: yes;"> </span>Potassium
can be replaced in a variety of formulations.<span style="mso-spacerun: yes;">
</span>The most common form is potassium chloride, which is sold in its generic
form or as <b style="mso-bidi-font-weight: normal;">Klor-Con</b>, <b style="mso-bidi-font-weight: normal;">K-Tab</b> or <b style="mso-bidi-font-weight: normal;">K-Sol</b> (there are probably other names, too).<span style="mso-spacerun: yes;"> </span>Every person needs a different amount of
potassium replacement based on their labs.<span style="mso-spacerun: yes;">
</span>Potassium is also available in combination with other essential
medications, including citrate and phosphorus.<span style="mso-spacerun: yes;">
</span>Side effects include nausea and abdominal discomfort. <o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Citrate:</b>
People with cystinosis lose bicarbonate in their urine, and this leads to more
acid in the blood (acidosis).<span style="mso-spacerun: yes;"> </span>The extra
acid is buffered by bone, which leads to poor growth, bone resorption and soft
bones (osteopenia).<span style="mso-spacerun: yes;"> </span>This is corrected by
taking a medication like citrate.<span style="mso-spacerun: yes;">
</span>Citrate is taken up in the liver and converted to bicarbonate.<span style="mso-spacerun: yes;"> </span>Citrate is combined with either potassium, sodium
or both.<span style="mso-spacerun: yes;"> </span>Potassium citrate is sold as <b style="mso-bidi-font-weight: normal;">Cytra-K</b>, <b style="mso-bidi-font-weight: normal;">Virtrate-K</b>, <b style="mso-bidi-font-weight: normal;">Polycitra-K</b>
and <b style="mso-bidi-font-weight: normal;">Urocit-K</b>.<span style="mso-spacerun: yes;"> </span>Some people get all of their potassium
replacement from potassium citrate.<span style="mso-spacerun: yes;">
</span>Sodium citrate is sold as <b style="mso-bidi-font-weight: normal;">Cytra-2</b>,
<b style="mso-bidi-font-weight: normal;">Virtrate-2, Oracit</b> and <b style="mso-bidi-font-weight: normal;">Bicitra</b> and does not have any potassium
in it. <b style="mso-bidi-font-weight: normal;">Tricitrates, Polycitra </b>and <b style="mso-bidi-font-weight: normal;">Cytra-3</b> have both potassium and sodium.<span style="mso-spacerun: yes;"> </span>Citrate does bind calcium, so large doses
can potentially lead to low calcium in the blood, which can cause tetany.<span style="mso-spacerun: yes;"> </span>This may be exacerbated if taken with other
medications that bind calcium, such as phosphorus. <o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Sodium bicarbonate: </b>This is essentially baking soda, and can be taken as a tablet, or as
actual baking soda in patients who cannot take or afford tablets.<span style="mso-spacerun: yes;"> </span>Just like citrate, this medication increases
serum bicarbonate levels to buffer the acids in the blood.<span style="mso-spacerun: yes;"> </span>It may be used in place of citrate, or in
addition to citrate. <o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Phosphorus:</b>
People with cystinosis lose phosphorus in their urine.<span style="mso-spacerun: yes;"> </span>Phosphorus is essential for building bone,
and low phosphorus (hypophosphatemia) leads to rickets, or soft bones.<span style="mso-spacerun: yes;"> </span>Phosphorus is available in many
formulations.<span style="mso-spacerun: yes;"> </span>It is combined with sodium
and potassium in <b style="mso-bidi-font-weight: normal;">Phos-NaK, K-Phos
Neutral, K-Phos No. 2, Phospha 250 Neutral, Virt-Phos 250 Neutral </b>and<b style="mso-bidi-font-weight: normal;"> Av-Phos 250 Neutral.</b><span style="mso-spacerun: yes;"> </span>It can also be prescribed as simply sodium
phosphate or potassium phosphate.<span style="mso-spacerun: yes;"> </span>Common
side effects include diarrhea and nausea.<span style="mso-spacerun: yes;">
</span>Large doses of phosphate taken at once can cause tetany by dropping
serum calcium levels.<o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Carnitine</b>:
This is another molecule that is lost in the urine in people with
cystinosis.<span style="mso-spacerun: yes;"> </span>Carnitine is required for
muscles to metabolize fat.<span style="mso-spacerun: yes;"> </span>Lack of
carnitine leads to accumulation of fat in muscle tissue and resultant myopathy
(muscle disease).<span style="mso-spacerun: yes;"> </span>Giving patients
carnitine supplements reduces accumulation of fat in muscle tissue.<span style="mso-spacerun: yes;"> </span>This drug is sold as Carnitor or
Levocarnitine. <o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Vitamin D</b>: <span style="mso-spacerun: yes;"> </span><span style="background: white; color: black;">Normally we make vitamin D in our skin, with
exposure to sunlight. We can also get vitamin D from fortified foods, or
from supplements. If the supplement is from a plant, it's called <span style="mso-bidi-font-weight: bold;">ergocalciferol</span>, or <span style="mso-bidi-font-weight: bold;">D2</span>. If it's from animals or our
skin, it is called <span style="mso-bidi-font-weight: bold;">cholecalciferol</span>,
or <span style="mso-bidi-font-weight: bold;">D3</span>. Whether we
make it in our skin or take a supplement, the vitamin D is modified by the
liver to make <span style="mso-bidi-font-weight: bold;">25-Vitamin D.</span>
This form of vitamin D is then modified again by the kidneys, to<b> </b><span style="mso-bidi-font-weight: bold;">make 1,25-Vitamin D,</span> which is the
active form. This form is also called <span style="mso-bidi-font-weight: bold;">calcitriol</span>, and it is required to maintain calcium and phosphate
levels in the blood and promote bone growth and remodeling. <span style="mso-bidi-font-weight: bold;">1,25-Vitamin D</span> increases
absorption of calcium and phosphate in the intestines.<span style="mso-spacerun: yes;"> </span>Dr. Mak, a CRF funded researcher, has shown
that 25-Vitamin D is important for muscle health. <o:p></o:p></span></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;"><span style="background: white; color: black;">Calcitriol</span></b><span style="background: white; color: black;">: This is the activated form of
vitamin D, also called 1,25-Vitamin D.<span style="mso-spacerun: yes;">
</span>In people with chronic kidney disease, the kidneys lose the ability to
convert 25-Vitamin D to the active form.<span style="mso-spacerun: yes;">
</span>This drug may also be prescribed in patients with severe hypophosphatemia
(low phosphorus) because it stimulates intestinal absorption of
phosphorus.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;"><span style="background: white; color: black;">Iron:</span></b><span style="background: white; color: black;"> People with cystinosis may
develop iron deficiency.<span style="mso-spacerun: yes;"> </span>Iron is
normally found in red meat, sea food, beans, spinach and peas.<span style="mso-spacerun: yes;"> </span>Iron is an essential element for making hemoglobin,
which is the protein in red blood cells that binds oxygen.<span style="mso-spacerun: yes;"> </span>Lack of iron leads to anemia.<span style="mso-spacerun: yes;"> </span>Iron may be taken as ferrous sulfate, ferrous
fumarate and ferrous gluconate.<span style="mso-spacerun: yes;"> </span>The
most common side effect is constipation, and it may make stools darker.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Thyroid hormone: </b>Cystinosis causes thyroid disease through a few mechanisms, including
cystine accumulation.<span style="mso-spacerun: yes;"> </span>Symptoms of low
thyroid (hypothyroidism) include fatigue, swelling, constipation, cold
intolerance, coarse hair and skin.<span style="mso-spacerun: yes;">
</span>Usually around age five to ten years, people with cystinosis require
thyroid hormone replacement.<span style="mso-spacerun: yes;"> </span>This is
typically done with levothyroxine, which is an analog of thyroxine, or T4.<span style="mso-spacerun: yes;"> </span>T4 is taken up by the body and converted to
triiodothyronine, or T3, the active form of thyroid hormone.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Growth hormone: </b>Many people with cystinosis have growth failure and are treated with
growth hormone.<span style="mso-spacerun: yes;"> </span>This drug is usually
given as a daily injection.<span style="mso-spacerun: yes;"> </span>It must be
given before the epiphyses (growth plates) fuse during puberty.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
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<br /></div>
<div class="MsoNormal">
<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Testosterone:</b>
Cystine accumulation and fibrosis in the testicles may lead to hypogonadism,
and some boys may need testosterone replacement in order to progress through
puberty.<span style="mso-spacerun: yes;"> </span>This can be administered as an
injection, implant, gel or patch. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Insulin: </b>Insulin
is a hormone produced by the pancreas to help cells take up glucose from the
blood.<span style="mso-spacerun: yes;"> </span>Many people with cystinosis
develop diabetes mellitus as teenagers or later due to the effects of
cystinosis on the pancreas.<span style="mso-spacerun: yes;"> </span>These people
have insufficient insulin production and require insulin therapy to maintain
normal blood sugars.<span style="mso-spacerun: yes;"> </span>Insulin is
administered as an injection.<span style="mso-spacerun: yes;"> </span>There are
long acting forms of insulin, such as glargine, that are given once a day.<span style="mso-spacerun: yes;"> </span>There are short-acting forms of insulin, such
as lispro or aspart, that are given with meals. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Proton pump inhibitor</b>: This class of medications includes esomeprazole, omeprazole,
lansoprazole and pantoprazole, among others.<span style="mso-spacerun: yes;">
</span>These medications lower the acidity of the stomach, which helps symptoms
of acid reflux and stomach ulcers.<span style="mso-spacerun: yes;"> </span>Many
people are put on these medications to help with the side effects of other
medications, including cysteamine.<span style="mso-spacerun: yes;">
</span>Because these medications make the stomach less acidic, people taking
Procysbi may want to avoid them.<span style="mso-spacerun: yes;"> </span>Some
research has shown that long term use of proton pump inhibitors is associated
with increased risk of fractures, low magnesium levels, B12 deficiency and
gastrointestinal infections. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">ACE inhibitors</b>:
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fosinopril and others.<span style="mso-spacerun: yes;"> </span>These medications
affect the renin-angiotensin-aldosterone system, which regulates blood
pressure, sodium and fluid status, and filtration through the kidneys.<span style="mso-spacerun: yes;"> </span>These drugs are used primarily for high blood
pressure and proteinuria (protein in the urine).<span style="mso-spacerun: yes;"> </span>Most if not all people with cystinosis have
protein in their urine. <span style="mso-spacerun: yes;"> </span>Because of
Fanconi syndrome, small proteins that are filtered through the glomerulus are
not reabsorbed by the proximal tubule.<span style="mso-spacerun: yes;"> </span>Research
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this leads to leaking of larger proteins, like albumin, into the urine.<span style="mso-spacerun: yes;"> </span>This usually manifests as foamy urine.<span style="mso-spacerun: yes;"> </span>Over time this causes further damage to the
kidneys.<span style="mso-spacerun: yes;"> </span>ACE inhibitors can be used to
reduce the amount of protein that leaks through the glomerulus by reducing the
pressure on the filtering system.<span style="mso-spacerun: yes;"> </span>Side
effects include low blood pressure and high potassium levels.<span style="mso-spacerun: yes;"> </span>Some people develop a chronic cough that
usually resolves after stopping the medication.<span style="mso-spacerun: yes;">
</span>Rarely people have a reaction in which the face or airway swells, called
angioedema, and this is an emergency.<span style="mso-spacerun: yes;">
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vomiting or diarrhea, because it can cause an acute kidney injury.<span style="mso-spacerun: yes;"> </span>In patients who have proteinuria but cannot
take an ACE inhibitor because of side effects or allergy, another class of
medications, called angiotensin receptor blockers, or ARBs, can be used.<span style="mso-spacerun: yes;"> </span>This class includes losartan, valsartan, irbesartan
and others. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Spironolactone: </b>This medication blocks the effects of a hormone called
aldosterone.<span style="mso-spacerun: yes;"> </span>It is a weak diuretic and
can cause dehydration and low blood pressure.<span style="mso-spacerun: yes;">
</span>Its main side effect is that it raises potassium levels, which may be
beneficial in people with cystinosis.<span style="mso-spacerun: yes;"> </span>It
also reduces the amount of protein that leaks into the urine, and may be
prescribed for this purpose.<span style="mso-spacerun: yes;"> </span>Other side
effects are related to its anti-androgen properties; it can cause menstrual
irregularities and breast tenderness/enlargement in men and women.<span style="mso-spacerun: yes;"> </span>Other related medications include amiloride
and eplerenone.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Indomethacin: </b>This
is a non-steroidal anti-inflammatory drug (NSAID) related to ibuprofen and
naproxen.<span style="mso-spacerun: yes;"> </span>Indomethacin reduces the
amount of blood that filters through the kidneys, which results in less urine
production.<span style="mso-spacerun: yes;"> </span>The drug is used to reduce
polyuria and improve electrolyte retention.<span style="mso-spacerun: yes;">
</span>Its use is controversial in people with cystinosis because NSAIDs are toxic
to the kidneys and can worsen renal failure.<span style="mso-spacerun: yes;"> There is some new data, however, that indomethacin may actually be protective in cystinosis. </span>You should not take this medication if you are dehydrated, as may occur
with vomiting and diarrhea, because it can cause an acute kidney injury.<span style="mso-spacerun: yes;"> </span>This drug can also cause ulcers in the
stomach and duodenum, so a proton pump inhibitor is usually prescribed with it
to reduce acidity in the stomach. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: "trebuchet ms" , sans-serif; font-size: small;"><b style="mso-bidi-font-weight: normal;">Ondansetron:</b>
This drug is also known as Zofran, and was developed to treat nausea and
vomiting associated with chemotherapy.<span style="mso-spacerun: yes;">
</span>Other drugs in this class include dolasetron and granisetron.<span style="mso-spacerun: yes;"> </span>Many people with cystinosis take this
medication to treat the side effects of medications they take, including
cysteamine.<span style="mso-spacerun: yes;"> </span>Common side effects include
headache and constipation.<span style="mso-spacerun: yes;"> </span>This medication
is known to cause QT prolongation on ECGs, which can lead to arrhythmias, so it
is important for your doctor to review possible medication interactions before
starting this drug.<o:p></o:p></span></div>
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<span style="font-size: small;"><b><span style="font-family: "trebuchet ms" , sans-serif;">Erythropoiesis-Stimulating Agents (ESA):</span></b><span style="font-family: "trebuchet ms" , sans-serif;"> The kidneys are responsible for monitoring oxygen
levels and telling the bone marrow when to make more red blood cells. As kidney disease progresses, this function
is lost, and many people develop anemia.
There are drugs, including Epoetin alfa (marketed as Procrit or Epogen)
and Darbepoetin alfa (marketed as Aranesp) that can be given to stimulate red
blood cell production in the bone marrow.
These drugs are given as an injection. </span></span><b style="font-size: 11.5pt;"><o:p></o:p></b></div>
stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-52448307786591858582017-05-03T20:46:00.003-07:002017-05-03T20:46:50.740-07:00Ashton's Speech for the Natalie's Wish Event 2017<div class="MsoNormal">
<span style="font-family: Trebuchet MS, sans-serif;">Here are the full remarks that Ashton gave at this year's Natalie's Wish Event:</span></div>
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<span style="font-family: Trebuchet MS, sans-serif;"><br /></span></div>
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<span style="font-family: Trebuchet MS, sans-serif;"><br /></span></div>
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<span style="font-family: Trebuchet MS, sans-serif;"><br /></span></div>
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<span style="font-family: Trebuchet MS, sans-serif;">A few weeks ago my four-year-old,
Lars, who has cystinosis, got home from pre-school and asked me “Mom, did you
know that there are kids in my class who don’t swallow pills? Ever?!” With a huge
smile on his face he asked me when he could stop taking medicine. It hurt my heart to tell him that the 16 big blue
pills he swallows every day are essential to keeping his body healthy. <o:p></o:p></span></div>
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<br /></div>
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<span style="font-family: Trebuchet MS, sans-serif;">Lars has a seven-year-old brother
who has charted the cystinosis path before him.<span style="mso-spacerun: yes;">
</span>Samuel was diagnosed with cystinosis when he was just a year old.<span style="mso-spacerun: yes;"> </span>Lars was only two when he watched his cool
older brother swallow over 20 pills each morning before school.<span style="mso-spacerun: yes;"> </span>Lars was determined to be like his brother and
learn to swallow pills.<span style="mso-spacerun: yes;"> </span>He started practicing
with mini m&m’s and never gave up.<span style="mso-spacerun: yes;">
</span>Before long he was swallowing 5 cystagon pills every six hours. <span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
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<br /></div>
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<span style="font-family: Trebuchet MS, sans-serif;">Some days the boys make it look
easy but it never really is. <span style="mso-spacerun: yes;"> </span>My husband
and I make up crazy stories and pretend pills are dinosaur eggs and Lars is the
T-rex coming to eat them.<span style="mso-spacerun: yes;"> </span>If that
doesn’t work, we’ll pretend that the blue pills contain super powers and the
white pills are alligator teeth.<span style="mso-spacerun: yes;"> </span>Other times
I will sit with the boys for 30 minutes coaching, encouraging, begging and sometimes
bribing them to take their medicine on schedule. Some days are especially hard
because their stomachs are aching, they have already thrown up once or twice,
and they are just plain tired of swallowing pills. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: Trebuchet MS, sans-serif;">I wish that the pills they take
each day could make them feel better immediately. <span style="mso-spacerun: yes;"> </span>Then they would more easily understand how
important the medicine is to keep them healthy. Unfortunately, every medication
has side effects, and more often than not the pills make the boys feel worse. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: Trebuchet MS, sans-serif;">Take potassium, for example.<span style="mso-spacerun: yes;"> </span>Because children with cystinosis lose so much
potassium in their urine, we have to give Sam enormous doses to keep his
potassium levels in the normal range.<span style="mso-spacerun: yes;"> </span>Each
month I pick up a grocery bag filled with eight large bottles of potassium chloride
from the Primary Children’s Hospital pharmacy.<span style="mso-spacerun: yes;">
</span>More than once the pharmacy technician has made me wait while a
concerned pharmacist calls our nephrologist to confirm that Sam really takes
the absurd amount of potassium prescribed for him. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: Trebuchet MS, sans-serif;">The potassium supplements upset
Sam’s stomach.<span style="mso-spacerun: yes;"> </span>He has thrown up many
times at school but tells me it’s okay because it’s almost always underneath
the playground where nobody can see.<span style="mso-spacerun: yes;"> </span>I
used to assure him that kids don’t remember those things until I introduced him
to our new neighbor who said, “Yeah, I know him.<span style="mso-spacerun: yes;"> </span>He’s the kid who threw up in the lunchroom.”<span style="mso-spacerun: yes;"> </span><span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: Trebuchet MS, sans-serif;">Some of my hardest moments as a
mother are when my children come home from school and tell me about an incident
where a kid has made fun of them because of the way they smell. Cysteamine
produces a rotten egg smell that I’ve had other kids describe to me as “fishy,”
“sour milk,” “dirty,” and my favorite, “Mmmmm, like spaghetti dinner.”<span style="mso-spacerun: yes;"> </span>Though most kids mean no harm, it makes me
sad to know that my kids have to experience this scrutiny regularly.<span style="mso-spacerun: yes;"> </span>I wish kids could see how strong and brave
Sam and Lars truly are for battling cystinosis every day. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: Trebuchet MS, sans-serif;">When Sam was first diagnosed
almost seven years ago, some people told us to never use the word “cure,”
because it was unrealistic and would spread false hope.<span style="mso-spacerun: yes;"> </span>After attending our first Cystinosis Research
Foundation conference, however, we were inspired by the dedication and perseverance
of the Stack family and Dr. Stephanie Cherqui, and we left filled with hope
that we really can beat this disease. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-family: Trebuchet MS, sans-serif;">We are so grateful to Nancy and
Jeff Stack, and to all of you, who generously support this cause.<span style="mso-spacerun: yes;"> </span>It is your encouragement and love that I
remember in moments when I feel like this disease is a burden too heavy to
bear.<span style="mso-spacerun: yes;"> </span>I hope that one day I will be able
to look at my son Lars and tell him he doesn’t have to take pills anymore.<span style="mso-spacerun: yes;"> </span>Thank you.<span style="mso-spacerun: yes;">
</span><o:p></o:p></span></div>
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stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com0tag:blogger.com,1999:blog-590688824130380762.post-5133206427859031602017-04-06T14:26:00.001-07:002017-05-03T20:42:13.752-07:00CRF Day of Hope 2017<div class="separator" style="clear: both; text-align: center;">
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span>
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Apparently it's been exactly one year since we last posted anything! We just returned from the 2017 Day of Hope family conference, and we wanted to share what we learned. This was the second year having the conference at the Island Hotel. Fortunately the weather was much better than last year, so we were able to spend more time outside!</span><br />
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span>
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We kicked off the conference on Thursday night with introductions. Old and new families got up to introduce themselves and to share their wishes. It was a great way to get to know people before having dinner that night. </span><br />
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span>
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Friday morning we started off with a welcome talk from Nancy Stack. She shared the many milestones the CRF has accomplished since it started back in 2003. The CRF has raised over $35 million for cystinosis research, funding more than 150 grants with over 67 publications. The CRF funded the original research for Procysbi, the 12 hour form of cysteamine, which was approved back in 2013. They have also funded Dr. Stephanie Cherqui's stem cell research from the beginning.</span><br />
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span>
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Nancy, I briefly spoke about the basics of cystinosis pathophysiology and history. Beyond Fanconi syndrome, corneal disease and muscle wasting, cystinosis also affects the thyroid, pancreas, reproductive organs, liver, heart, lungs and brains. This is why any attempt to cure the disease will have to be multi-systemic and involve correcting the defective cystinosis gene.</span><br />
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span>
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next Dr. Grimm from Stanford talked to us about Fanconi syndrome, which is caused by destruction of the proximal tubules of the kidneys. These tubules are responsible for reabsorbing the electrolytes, nutrients and fluid that are filtered by the kidneys. Damage to the proximal tubules results in excessive thirst and urination because of fluid losses. It also leads to low potassium, low bicarbonate (acidosis), low phosphorus (which leads to rickets), and loss of glucose, amino acids and proteins. Dr. Grimm talked about dosing citrate (or bicarbonate) 3-4 times a day to improve acid levels in the blood. Citrate is converted to bicarbonate by the liver. Dr. Grimm pointed out that it's okay to take citrate with Procysbi, but not bicarbonate (bicarbonate is basic and will dissolve the Procysbi beads prematurely). He also recommended not taking calcium and phosphorus at the same time, since they can precipitate in the gut, preventing absorption of both. Dr. Grimm also shared some retrospective data from Dr. Emma in Italy that suggests indomethacin, which is used routinely in Europe, may be beneficial for growth and protective to the kidneys. This generated a lot of excitement and questions from many families.</span><br />
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span>
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Mak from UCSD talked next about his research on the effects of inflammation on the kidneys and muscles. He has shown that mice with cystinosis have activation of inflammatory pathways mediated by a receptor called NLRP3, which leads to production of a cytokine called interleukin-1 (IL-1), and this may contribute to myopathy and chronic kidney disease. Some of this inflammation may be reversed by repleting vitamin D. He has created a knockout mouse that is missing the cystinosin gene and the gene for NLRP3, which eliminated this inflammatory pathway. These mice still have cystinosis, but they have improved muscle mass and strength, and they don't have Fanconi syndrome. There is a drug called anakinra which blocks IL-1, and he is going to test this drug on mice with cystinosis to see whether it improves kidney function and muscles. </span><br />
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;"><br /></span>
<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Mak we heard an update from Dr. Mary Leonard from Stanford. She has finished the study on bone and muscle disease and is still compiling and analyzing data. She found that bone mineral density was very low in cystinotic bones, with more than half the participants with BMD below the 15th percentile for age. Cystinotic bones were more fragile, with a thinner cortex and more porosity. She thinks this is most likely due to muscle disease. Muscle mass in the limbs was also significantly reduced. More than half the participants had muscle mass less than 10th percentile for age. She is now going to look at a number of lab markers for bone disease, including vitamin D metabolites, PTH, FGF-23 and cytokines to see whether there are clues for pathophysiology and therapeutic targets. She recommended weight bearing exercise, like running or soccer, to help build bones, as well as making sure phosphorus, calcium and vitamin D levels are normal. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Simpson at UC-Irvine. She spoke about the many ways cystinosis can affect the eyes, beyond just corneal disease. Cystinosis can affect the tear film and conjuctivae to cause dry eye and filamentary keratitis. Cystinosis can also affect the iris, leading to angle-closure glaucoma, which is an emergency. Dr. Simpson pointed out that corneal cystinosis should not cause vision loss, so if you have new vision problems you need to be evaluated for a different cause, such as retinal disease, cataracts, glaucoma or optic nerve problems. Cystinosis can affect the optic nerve through something called pseudotumor cerebri, in which there is too much cerebrospinal fluid production. This can cause headache and blindness, and is detected by a dilated eye exam showing papilledema. Regarding corneal cystinosis, Dr. Simpson recommended monitoring corneal cystine burden with optical coherence tomography, which is more objective then slit-lamp exams. She recommended starting Cystaran drops as soon as a child can tolerate them.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Simpson we heard from her husband Dr. Ron Kurtz, who is helping lead the cystine nanowafer project. The nanowafer was developed by Dr. Ghanashyam Acharya with Dr. Simpson. The CRF has the license of the nanowafer and is meeting with the FDA soon to file an IND application to start a clinic trial, hopefully this year.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Morgan Fedorchak from University of Pittsburgh. She has developed a novel way to treat corneal cystinosis. She created microspheres out of PLGA with cysteamine inside. These microspheres are dissolved by the tears. The microspheres are suspended in a hydrogel. The hydrogel is applied as an eye drop, but when it hits the eye it forms a semi-solid gel that sits under the bottom eyelid. The gel then slowly elutes the drug. She has designed a similar gel for glaucoma that can be applied every 28 days. She anticipates this new hydrogel could be put in once a week or once a day. This type of drug would not require benzalkonium chloride, which is the preservative found in Cystaran eye drops (which can cause irritation and allergic reactions). She is hopeful that a clinical trial can happen in the next couple years! </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Fedorchak we heard from Dr. Sergio Catz from Scripps. He talked about a protein called LAMP2A that acts as a port of entry to the lysosome. It's an important receptor in chaperone-mediated autophagy. It's built somewhere else in the cell and has to be transported on the cellular highway to the lysosome. When the protein cystinosin is absent, LAMP2A has difficulty getting to the lysosome, and this leads to a build-up of junk outside the lysosome. This can be just as disruptive as stuff building up inside the lysosome (i.e. cystine) and leads to increased cellular stress. He is collaborating with another reseacher, Ana Maria Cuervo, at Albert Einstein College of Medicine. She has already found some molecules that stabilize LAMP2A, improve its trafficking to the lysosome and reduce cellular stress. They are testing these molecules in cystinosis mice. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Stephanie Cherqui about the upcoming stem cell trial. She has shown that you can remove stem cells from mice with cystinosis and genetically modify them to insert a functional cystinosis gene. These stem cells can be given back to the mice as a transplant, and these stem cells rescue organ function in the mice, effectively curing them. She is hoping to file the IND with the FDA this year, and we may be able to start the trial soon after that. For the trial, patients will come to UCSD for a full evaluation by multiple physicians. They will undergo numerous tests to assess baseline organ function before the trial. Then they will be given G-CSF, which stimulates the bone marrow to produce new cells. Stem cells will be harvested from the patient through cell apharesis. These cells will then be sent to Dr. Kohn at UCLA to be modified. This process takes 3-4 months, so the patients will go home for that period. After the cells have been successfully modified, the patients will return to UCSD for the transplant. They will receive a chemotherapy called busulfan to ablate the bone marrow, then they will receive the stem cell transplant through an IV. They will then remain in the hospital for one month awaiting return of their bone marrow and immune system. During this month they will be at very high risk for infection. After that they will be discharged from the hospital but will need to stay in San Diego for another two months because they will require weekly visits for testing. Six months after the transplant they will return to San Diego and have a full evaluation to determine whether the transplant worked. They will return every 6 months for two years after the transplant. There will be 2 adults in the first phase, then 2 more adults. If the trial goes well they will open it up to adolescents for the last 2 participants. I'm so excited to see who will go first! </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Cherqui we heard from Tatiana Lobry, a PhD student in Dr. Cherqui's lab. She actually has a sister with cystinosis, which makes her even cooler. She is researching the role of inflammation in the kidney disease of cystinosis. She has identified a protein called galectin-3 that is overexpressed in cystinosis knockout mice. This protein is involved in a pathway that recruits inflammatory cells. She has created a double knockout mouse that is missing the cystinosis gene and the gene for galectin-3. These mice have better kidney function than single cystinosis knockout mice, suggesting that inflammation is contributing to their kidney disease. There are drugs in the pipeline that block galectin-3, and these may have a role in treating cystinosis in the future. She also noted that indomethacin, a non-steroidal anti-inflammatory medicine, inhibits transcription factors that are implicated in galectin-3 expression. This raises the consideration that indomethacin may protect the kidneys by reducing inflammation. Pretty cool!</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Bruce Barshop from UCSD. He talked about the new cystine test and addressed the concerns of many families who reported getting higher levels lately. As he has said before, the new target number is less than 1.9. He said that when you scale the numbers people are getting compared to the previous test, the variability is actually better with the new test. He also reiterated that the blood test should be drawn BEFORE you take your next dose of Procysbi or Cystagon (this is different than the Procysbi trial). </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Barshop we heard from Dr. Patrice Rioux and Dr. Vincent Stanton, who are working on new pro-drugs for cysteamine. Dr. Rioux helped design Procysbi and used to work for Raptor Pharmaceuticals. He and Dr. Stanton have formed a new company called Thiogenesis Therapeutics. Cysteamine is rapidly metabolized and has be to dosed multiple times a day. The peaks associated with the medication cause significant side effects, like nausea, vomiting and a sulfurous smell. They are working on precursors that could be slowly converted to cysteamine in the intestines. They would maintain a lower basal rate of cysteamine, hopefully avoiding the side effects associated with the peaks. They would also hopefully extend the time between doses. They felt like they could have a trial in the next couple years. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">On Friday night we got on fancy buses and headed to "the Dunes," a nice beachfront venue for dinner. There was a gourmet macaroni and cheese bar, with all sorts of yummy barbecued meat. For dessert we had cupcakes and a s'more bar. The kids had fun running around on the beach with little flashlights. Only a few got wet :) </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Saturday morning we resumed the conference bright and early with a session by Dr. Grimm. He talked about how siblings of children with chronic illnesses cope. He also talked about the issues of medication compliance in adolescence, and how to let your teenager grow and take responsibility for their own care. The highest risk of losing a kidney transplant is age 19-21 because of medication non-adherence. Knowing how stubborn my children are now, I can only imagine what it will be like to have teenagers. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Grimm we heard from Dr. Doris Trauner from UCSD. She talked about the many neurological complications of cystinosis. She also talked about sleep disturbances in cystinosis, and how this may affect memory and mood. She is doing a study on sleep disturbances in cystinosis and needs adult volunteers. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Ilya Gerstman, who works in Dr. Barshop's lab. He acknowledged that the white blood cell cystine test is error-prone and only captures a moment in time. It would be better to have a different lab test to monitor disease control. He is using a process called metabolomics to analyze thousands of metabolites in the blood that could be used to monitor the therapeutic effects of cysteamine and the effects of cystinosis on the body over time. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After that we had our physician/scientist panel where people could ask questions about the research and about their own children. People had a lot of questions about indomethacin. The data about this drug aren't published yet, so it may be hard to convince your nephrologist that a historically toxic medication may actually protect the kidneys. People also asked a lot about knock knees, flat feet, and bone pain. Dr. Leonard thinks a lot of the bone problems are actually secondary to muscle disease. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After that panel we heard from the adults with cystinosis panel. It was inspiring to hear about how they have overcome many of the challenges and obstacles of cystinosis. They were candid and honest about their fears, and they all expressed cautious optimism for the future, especially regarding the stem cell transplant trial.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Saturday night we all attended the Natalie's Wish Gala. There were over 475 people there. Ashton was asked to speak about Sam and Lars and our cystinosis journey. She did a fantastic job. I'll post her speech separately. That night the CRF raised a record-breaking $3.5 million (last year was $3.3. million!). It was amazing to see so many generous people donate to a cause that doesn't affect them personally. It was an inspiring evening for everyone. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Now only 365 days till the next conference! We're already counting down the days . . . </span><br />
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stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-63589532298851191392016-04-11T22:17:00.000-07:002016-04-11T22:22:23.952-07:00CRF Day of Hope 2016<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We just got back from another amazing Cystinosis Research Foundation family conference. There were 240 people there! With so many people and new families, the CRF actually moved locations to the Island Hotel. We missed the Balboa Bay Resort, but the Island Hotel was beautiful and very accommodating. They even gave us a discounted laundry rate to take care of our bedding every morning!</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">The conference started with a welcome dinner on Thursday night. We connected with old friends and met a lot of new ones. It didn't take long (about the time it takes to eat two quesadillas) before the boys were running wild with all of their friends. Sam quickly found Henry Sturgis, his favorite pal, and Lars ran along after them. Playtime was only interrupted by a few handfuls of Procysbi, and they were ready to keep going. We tried to go to bed a little early, knowing that our conference would commence bright and early. </span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We kicked off the meeting with family introductions. Everyone stood and shared a little of their story. We all wrote down our wishes for our children and loved ones with cystinosis, and we posted them on a giant kaleidoscope heart. There were a lot of tears and laughs and hope shared. It was cool to see some new adults with cystinosis introduce themselves and share a little of their journey with the group. It felt like a big family reunion. </span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Nancy Stack started the next session with a talk about the Cystinosis Research Foundation, which since 2003 has raised over $30 million dollars. They have funded 134 multi-year research grants in 12 countries, with 62 publications in prestigious journals. They funded the research that led to the development of delayed release cysteamine, Procysbi. They are the largest funder of cystinosis research in the world. </span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Sandra Amaral from Children's Hospital of Philadelphia attended this year, and gave a talk about Fanconi Syndrome. She explained the mechanism of how cystinosis causes damage to the proximal tubule of the kidney, so it is unable to reabsorb important electrolytes, proteins and sugar. She talked about the many medications that people with Fanconi's syndrome must take, including potassium, citrate, phosphorus and others. She made the interesting point that phosphorus and calcium should not be taken at the same time because they bind each other in the gut, which impairs their absorption. Later in the conference she gave a talk about adolescents and adults with cystinosis, and the special challenges that go along with transplant, medication adherence, education, and work. She addressed strategies for coping and improving quality of life and recommended a book called <i>Building Resilience in Children and Teens: Giving Kids Roots and Wings </i>by Kenneth Ginsburg. </span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Mary Leonard from Stanford gave us an update on her study of muscle and bone health. So far she has obtained data on 23 people with cystinosis, ages 8 to 49. Her preliminary data shows that people with cystinosis have much lower bone mineral density than average. More than half of study participants had bone mineral density less than the 10th percentile for age. She also found that people with cystinosis have significantly reduced muscle mass. More than half had less than the 5th percentile for age. She found that cystinosis bone is thinner, likely because of lack of muscle forces. She recommended weight-bearing exercise to help build stronger bone. It's also important to have enough phosphorus, calcium and vitamin D to build bone. There may also be a role for growth hormone to improve bone and muscle health. She also noted that two of the participants had unusually good bone mineral density, and this was associated with abnormal dentition. She and Dr. Grimm think this is likely secondary to fluoride toxicity. The increased bone mineral density in fluoride toxicity is actually unhealthy and is more likely to lead to fractures. Since patients with cystinosis drink such high volumes of water they may be at higher risk for excessive fluoride intake, so this is something they will look at in their study. </span></div>
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Mak provided a summary of many of his studies of muscle wasting in cystinosis. He showed his data on vitamin D, which I summarized in a <a href="http://littlebravesambo.blogspot.com/2014/04/vitamin-d-and-muscle-wasting.html" target="_blank">previous blog post</a>. The important thing is that over the counter vitamin D, either cholecalciferol or ergocalciferol, also known as 25-vitamin D, may help improve muscle mass and strength. This vitamin D is different than calcitriol (1,25-vitamin D) that many people with kidney disease require for bone health. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">He talked about cachexia, which is a nutritional wasting that is different than malnutrition. Even if you give patients with cystinosis adequate calories they fail to gain weight and build muscle. This process may involve the transformation of white fat to brown fat. Brown fat is something that babies need to stay warm because it burns calories to produce heat. This process is maladaptive in cystinosis because it wastes energy. Dr. Mak has shown that cystinosis mice develop more brown fat, and this is probably driven by increased cellular inflammation. His lab has found increased level of inflammatory cytokines in cystinosis mice, including interleukin-1. They are testing an anti-inflammatory drug that blocks interleukin-1 in cystinosis mice to see whether it reduces inflammation and improves muscle mass. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Another pathway involved in cachexia is leptin signaling. Leptin is a hormone that regulates appetite and is very important in regulating energy and metabolism. Dr. Mak and his lab have treated cystinosis mice with a leptin blocker, and they found that it reversed muscle wasting and improved muscle function. This is another exciting potential target to treat muscle wasting in cystinosis. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">After Dr. Mak we heard from Dr. Kate Dahl, a clinical psychologist from Stanford who specializes in child and adolescent psychiatry. She talked about the ways a medical diagnosis affects every member of the family and how it can trigger distress emotions. She talked about the different ways people cope with challenges and reviewed strategies to enhance coping and communication for caregivers and people with cystinosis. She walked us through a practice run in mindfulness training, and recommended a couple apps, including "Headspace" and "Calm." After her talk she conducted special sessions for adults with cystinosis and for caregivers of adults with cystinosis. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">While Dr. Dahl did her more private sessions, the rest of us had a forum on troubleshooting many of the daily challenges of cystinosis. We talked about ways to organize medications. Some people use color coding, others lettering systems. Many families draw up enough medications for a month so syringes are ready to go anytime. Denice Flerchinger recommended monoject slip tip syringes because the numbers never wear off. Nicole Manz talked about how to do a blended diet. We talked about getting a 504 plan for school in order to accommodate things like free access to the bathroom. We also talked about bedwetting, something we have continued to struggle with. I think the takeaway there was that the child will night train when they are ready, and in the mean time we should try to keep up with the laundry.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next we heard from Dr. Bruce Barshop of UCSD about the new cystine measurement assay. He explained how 1.9 became our new target for cystine levels. Apparently 99.9% of carriers (people with one cystinosis gene) have levels less than 1.9. This number also seems to correlate very well with 1.0 and the old test. He says that his lab will still run the old white blood cell cystine test if local labs are having difficulty, but the new test should be much easier. All you need is a yellow top tube, shipped overnight to UCSD on ice. He also clarified a very important thing that was a little confusing from the original trial. Blood should be drawn 12 hours after the last dose of Procysbi and 6 hours after the last dose of Cystagon, AND THEN the medication should be taken. Some patients would take the medicine and then get the blood drawn, but if there were delays in blood collection, then cystine levels could be falsely low. He also recommended that you get cystine checks at least 2-3 times a year, and much more frequently when converting from Cystagon to Procysbi.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Betty Cabrera from UCSD talked about the importance of registering and updating our profiles on CCIR. The survey has been updated with new questions that are relevant to upcoming clinical trials. It is a very important source of information for our researchers. She recommended that everyone try to update their profiles by May 1, or May Day. If you'd like to register or update your profile, go to the <a href="https://cystinosis.patientcrossroads.org/" target="_blank">CCIR website. </a></span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We capped off Friday's sessions with the Adult and Teen Panel where we got to hear from some of the giants in the cystinosis community. We heard enlightening insights about medication compliance, moving out, working and the hope they have for a cure. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">While we were at talks, the kids were having a blast with the babysitters. They had a great itinerary, including yoga training, a magician, and a visit from some wild animals. The kids got to pet a porcupine, a hedgehog, an armadillo, an alligator, a boa constrictor, and a kinkajou! Sam loved the endless potato chips and Lars was in juice heaven. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Friday night we had another wonderful dinner, and yes, there was cotton candy with light-up wands. I think Sam looks forward to that more than anything else. He and Henry immediately set to work gathering an army of boys and declared war on the girls. There was a little bit of chaos in the hotel lobby. The whole lightsaber battle worked better on the beach at Balboa Bay . . . </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Saturday morning was packed with translational research updates. We heard from Dr. Sergio Catz about a protein called LAMP2A that acts as a port of entry to the lysosome. It's an important receptor in chaperone-mediated autophagy. It's built somewhere else in the cell and has to be transported on the cellular highway to the lysosome. When the protein cystinosin is absent, LAMP2A has difficulty getting to the lysosome, and this leads to a build-up of junk outside the lysosome. This can be just as disruptive as stuff building up inside the lysosome (i.e. cystine) and leads to increased cellular stress. He is collaborating with another reseacher, Ana Maria Cuervo, at Albert Einstein College of Medicine. She has already found some molecules that stabilize LAMP2A, improve its trafficking to the lysosome and reduce cellular stress. They are testing these molecules in cystinosis mice. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Stephanie Cherqui gave an inspiring talk about the potential for stem cell transplantation to cure cystinosis <a href="http://littlebravesambo.blogspot.com/2014/10/how-to-cure-cystinosis.html" target="_blank">(see my old blog post here)</a>. She is almost done with the safety and toxicology studies. They have been working out the best way to transduce human stem cells with the lentivirus that holds the corrected cystinosin gene. Their protocol worked great in healthy human stem cells, but in cystinosis stem cells the lentivirus is not taken up as avidly. She is hoping to submit the IND (investigational new drug) paperwork and IRB this fall, and then we will anxiously wait for FDA approval to start the clinical trial. They will start with 2 adults, followed by another 2 adults. Then they will re-evaluate the safety of the treatment and consider 2 adolescents. The treatment will require a full month in the hospital, followed by weekly visits at UCSD for 2-3 months. The cure is coming!</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Dr. Cherqui was followed by her PhD student Spencer Goodman. He did a fantastic job explaining the mechanism by which hematopoietic stem cells can rescue organ function in cystinosis. Stem cells turn into macrophages, which transfer healthy lysosomes to cystinosis cells through tunneling nanotubules. This mechanism holds great potential for other organelle based diseases. To read more about macrophages and tunneling nanotubules, <a href="http://littlebravesambo.blogspot.com/2014/10/dr-cherqui-and-amazing-lysosome.html" target="_blank">check out my old blog post. </a></span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Next up we heard from Dr. Jennifer Simpson of UC-Irvine. She talked about how there is more to ocular cystinosis than corneal crystals. Every compartment of the eye is affected, including the retina, conjunctiva, iris and ciliary bodies. Patients with cystinosis are at high risk of dry eye because the goblet cells that secrete mucus, an important part of your tear film, are lost over time. She also noted that corneal crystals should not affect vision, so if your vision is worse than 20/30, then your ophthalmologist should look for another cause. She also talked about the risk of glaucoma, which is caused by increased pressure in the eye. This manifests as pain in the eye, redness, tearing, seeing halos, nausea and vomiting, and is an eye emergency. She also spent some time on pseudotumor cerebri, aka idiopathic intracranial hypertension, which has been seen in some patients with cystinosis. Increased intracranial pressure can damage the optic nerve, which carries visual signals from the eye to the brain. This damage can cause blindness. Any vision loss should involve evaluation of the optic nerve. She also talked about how optical coherence tomography (OCT) is superior to slit lamp exams for monitoring crystals in the cornea. She is working on cystinosis guidelines to share with our ophthalmologists.</span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Ghanashyam Acharya updated us on the nanowafer for corneal cystinosis, which is gearing up for a clinical trial. The nanowafer is like a very thin contact lens made of polyvinyl alcohol. It is 80 microns thick, compared to a contact lens which is 200 microns thick. The nanowafer is more effective than cysteamine drops and does not need to be refrigerated because the drug is more stable. It will also improve compliance significantly. He also gave us an update on the transdermal patch, which will pump cysteamine in through the skin. It would hopefully produce more steady drug concentration in the blood and have less side effects. He is currently testing it on cadaver skin and pigs! For more information on the cysteamine patch, <a href="http://littlebravesambo.blogspot.com/2014/04/ghanshyam-and-magical-cysteamine-patch.html" target="_blank">check out my old blog post. </a> </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">The final speaker was Doris Trauner, who summarized her findings of her study on quality of life and psychosocial functioning in teens and adults with cystinosis. She found that adults and teens with cystinosis have problems with sleep, anxiety, depression, fatigue and independence. They also reported strong emotional and family support. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">We concluded the session with a Q&A panel with the physicians and researchers. As in previous years people expressed interest in doing research on male fertility. There were several questions about medication compatibility. Procysbi should be taken with acids, like orange juice, and should not be taken with bicarbonate. </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">Saturday night was the big Natalie's Wish event. Twenty-one families presented checks to the CRF this year! We presented a check for over $24,000! The CRF brought in a record 3.3 million dollars that night, and the money keeps coming in! </span><br />
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<span style="font-family: "trebuchet ms" , sans-serif; font-size: large;">This year Rachel Platten, popular singer of "Fight Song" provided the entertainment. She met the kids before the event and took pictures. At the end of the gala she had all the kids come up to the stage to sing "Fight Song." There were a lot of tears. It was the perfect end to the perfect conference. We all left energized to keep fighting cystinosis every day. </span><br />
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stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com2tag:blogger.com,1999:blog-590688824130380762.post-20810719411084822832015-09-25T07:55:00.000-07:002016-04-12T09:24:31.150-07:00We Were on the News!You've probably already seen this, but in case you haven't, <a href="https://www.ksl.com/?sid=36630451&nid=148&title=salt-lake-family-fights-for-childrens-lives-with-courage-faith" target="_blank">check out the story</a> that Heather Simonsen from KSL 5 did on our family!<br />
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<br />stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-41060039931807732172015-09-14T08:11:00.001-07:002015-09-14T08:11:52.088-07:00Freshly Picked<div dir="ltr" style="line-height: 1.38; margin-bottom: 0pt; margin-top: 0pt;">
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<span style="background-color: transparent; color: black; font-family: Arial; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">When I reached out to <a href="http://freshlypicked.com/" target="_blank">Freshly Picked</a> and asked if they would donate to our fundraiser, I hoped they would send one pair of moccasins. When they sent four pairs, I was blown away by their generosity. Now I understand that it’s not just the unique, durable, and adorable product that endears Freshly Picked to its customers, but the brand’s generosity as well.</span></div>
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<span style="background-color: transparent; color: black; font-family: Arial; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Anything that can simplify our lives is something worth having, and Freshly Picked offers simplicity in spades. The soft leather is easy to clean and doesn’t give Lars any blisters. More importantly, Lars can put them on himself without having to worry about getting the correct shoe on the correct foot. Toddlers have a 50% chance of getting it right, but somehow manage to get the wrong shoe on the wrong foot 90% of the time. The design of Freshly Picked makes their lives, and their mothers’ lives, a little less frustrating. </span><br />
<span style="background-color: transparent; color: black; font-family: Arial; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;"><br /></span><span style="background-color: transparent; color: black; font-family: Arial; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Freshly Picked moccasins come in a variety of designs, from super girly to super masculine, and everything in between. Any child can be comfortable with the shoes’ fit and look.The winning bidders for moccasins will be able to choose the style and size from Freshlypicked.com</span><br />
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<span style="background-color: transparent; color: black; font-family: Arial; font-style: normal; font-variant: normal; font-weight: 400; margin-left: 1em; margin-right: 1em; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;"><img alt="Pineapple - Picnic Pack Limited Edition Moccasins" src="http://cdn.shopify.com/s/files/1/0204/2258/products/wc_FP_PicnicPack_V2_0829_grande.jpg?v=1433366372" height="200" width="200" /><img alt="Heirloom in Blush and Gold - FP Signature Moccasins" src="http://cdn.shopify.com/s/files/1/0204/2258/products/wc_FP_Heirloom_0854_large.jpg?v=1437516787" height="200" style="line-height: 1.38;" width="200" /><img alt="Beehive State - Utah Collection Moccasins" src="http://cdn.shopify.com/s/files/1/0204/2258/products/wc_FPUT14_OnWhite_20141223_2547_large.jpg?v=1423158265" height="200" style="line-height: 1.38;" width="200" /></span></div>
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<span style="font-family: Arial; vertical-align: baseline; white-space: pre-wrap;">We are incredibly grateful to Freshly Picked for so generously supporting this auction. Sam’s Hope for a Cure benefits greatly from the donations of local artists and companies like Freshly Picked. The money from the winning bid, as well as the money from all other auction items, will go to the Cystinosis Research Foundation. If you miss out on placing the winning bid for the moccs, we encourage you to visit <a href="http://freshlypicked.com/">freshlypicked.com</a> to find the perfect moccasins for your little one.</span><br />
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mildredhttp://www.blogger.com/profile/02034924909970073272noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-63894288638051025452015-09-14T07:15:00.001-07:002015-09-14T07:15:13.960-07:00Some of our 2015 Sponsors<div class="separator" style="clear: both; text-align: center;">
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<br />mildredhttp://www.blogger.com/profile/02034924909970073272noreply@blogger.com0tag:blogger.com,1999:blog-590688824130380762.post-14616697480587181632015-08-27T20:17:00.003-07:002015-08-27T20:18:10.732-07:00darth vader vs. darth vaderWe had fun making this movie. The Force is strong with this one.<br />
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<span id="goog_1327735219"></span><span id="goog_1327735220"></span><br />stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com0tag:blogger.com,1999:blog-590688824130380762.post-41847399814547674982015-08-18T22:25:00.003-07:002015-09-03T16:18:12.048-07:00Lars Dancing<div class="separator" style="clear: both; text-align: left;">
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Watch Lars dance for a good cause!stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-61656845005001087502015-08-18T22:09:00.002-07:002015-08-25T17:47:43.464-07:00Our new digs<div class="separator" style="clear: both; text-align: center;">
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<br />mildredhttp://www.blogger.com/profile/02034924909970073272noreply@blogger.com2tag:blogger.com,1999:blog-590688824130380762.post-46851854031139855702015-08-17T16:00:00.002-07:002015-08-17T16:00:19.193-07:00Sam and Lars CRF 2015 Outtakes<div class="separator" style="clear: both; text-align: left;">
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Many of you have seen the 2015 Cystinosis Research Foundation movie that featured our family. Lars Wanberg and his son made that movie, and they spent about a week with us in Salt Lake City filming for it. Lars was nice enough to make an outtakes movie for us with some of the footage that didn't make it into the final cut. Check it out!</span>stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-49881224981786665412015-07-22T19:44:00.000-07:002015-08-17T19:44:57.553-07:00a new start<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_nRk4yI3DbuC3hE9dKSOge4VJAwIq_m1Q1-JWT6t8G92lNnxqpE6rCVAKrJONhD1GJyBQwYzLNJHUijc-wV3Da2luP4ecge4wDzi-oaFFwXt-sP89jBSC55uGyoWU6yq_kWju6NfMeEg/s1600/IMG_1748.JPG" imageanchor="1" style="font-family: Verdana, sans-serif; font-size: x-large; margin-left: 1em; margin-right: 1em; text-align: center;"><img border="0" height="425" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_nRk4yI3DbuC3hE9dKSOge4VJAwIq_m1Q1-JWT6t8G92lNnxqpE6rCVAKrJONhD1GJyBQwYzLNJHUijc-wV3Da2luP4ecge4wDzi-oaFFwXt-sP89jBSC55uGyoWU6yq_kWju6NfMeEg/s640/IMG_1748.JPG" width="640" /></a><br />
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<span style="font-family: Verdana, sans-serif; font-size: large;">We haven't posted for a while because life has been crazy. We moved on July 11, and the dust is finally starting to settle. We loved our home in the Avenues, but we were outgrowing the space and needed a change of scenery. </span><br />
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<span style="font-family: Verdana, sans-serif; font-size: large;">We moved to Sugarhouse, the land of families with small children. I had heard about a certain rental from some other residents, so we called up the landlord and got on the waiting list back in January. We had given up hope on getting the place, but he called us in June to let us know the unit was available. We jumped at the chance and Ashton had the whole house packed in a week. The former tenants moved out June 30, and after some repairs and carpet cleaning the place was ours. We were lucky to have a lot of help from the 21st North Ward loading up the truck, and Ashton's and my family helped unload on the back end. Fortunately we don't have that much heavy furniture, just a lot of toys. So many toys. And now we finally have the space to play with them!</span></div>
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<span style="font-family: Verdana, sans-serif; font-size: large;">This place is amazing. It is a duplex that faces another duplex, with a long driveway in between that is almost as wide as a road. There are young families across from us, so there are kids outside ALL THE TIME. And the driveway is the perfect place to ride bikes, scooters, and anything else with wheels, as well as play basketball, soccer, baseball, and anything else you can think of. The boys have been in heaven with so many accessible playmates, and the neighbors have been so welcoming. On our third night there they threw a barbecue for us. </span></div>
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<span style="font-family: Verdana, sans-serif; font-size: large;">The house is a split-level, with three bedrooms and two bathrooms. We are excited to have a bathroom that doesn't require traversing our bedroom. There is a big playroom downstairs, and a nice laundry room (also an upgrade, for any of our friends who ever saw "Gitmo" in our last house). The kitchen is smaller and we miss our wood floors, but the extra space is making up for it.</span></div>
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<span style="font-family: Verdana, sans-serif; font-size: large;">We saw our nephrologist recently, and we finally have Sam off prednisone. We did the longest, slowest taper imaginable, and he is a much happier kid. It's nice to see his silly smile more often.</span></div>
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<span style="font-family: Verdana, sans-serif; font-size: large;">Sam had grown a little taller since our last appointment, but only gained 1 lb. He is soooo skinny. Gone are the chubby cheeks of prednisone. We had to put him back on the feeding pump at night time to get extra calories in. Our dietitian wants him to eat 1600 calories a day, which is quite a bit for a kid who used to be completely dependent on tube feeds. After the appointment we went to Costco to stock up on all of Sam's favorite fattening foods. His newest favorite is the parmesan garlic butter spread. He asks for garlic toast about 5 times a day. </span></div>
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<span style="font-family: Verdana, sans-serif; font-size: large;">Based on the last round of labs, his cystinosis is about where it's been. His WBC cystine test came back at 0.24, which is the best it's ever been on Procysbi. He's on 8 pills twice a day, though, which is quite a bit for his size, and it comes with a more noticeable sulfur smell. His potassium and bicarbonate are still on the low side, so we did have to raise Sam's potassium again. Potassium makes Sam really nauseous, and we have to give it to him every 6 hours. </span></div>
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<span style="font-family: Verdana, sans-serif; font-size: large;">The protein in his urine is still really high, this time around 4 g. I don't think the rituximab is working. I think all the benefit we've seen so far is from the lisinopril, which we are increasing to 2.5 mg twice a day. We can't really push that drug much more though because of blood pressure. The next step will be to check his B-cell counts. If those are creeping up again, we might do another round of rituximab. </span><br />
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<span style="font-family: Verdana, sans-serif; font-size: large;">If the B-cell counts remain low, however, and the proteinuria persists, then we have to try another medication. Our nephrologist is thinking tacrolimus, an immunosuppressant used for organ transplants. The drug has lots of downsides. The major one is tacro is toxic to the kidneys over time, and Sam's kidneys are already getting damaged by cystinosis and membranous nephropathy. Tacro levels also have to be monitored, which means more blood draws for Sam (he's tough, but they still suck). Another option would be mycophenolate mofetil (cellcept). That one isn't hard on the kidneys, but it does give people GI upset, and we have enough of that already. </span><br />
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stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com1tag:blogger.com,1999:blog-590688824130380762.post-63266505593487339292015-05-01T21:27:00.003-07:002015-05-01T21:30:29.263-07:00Is Rituximab Working?<div class="separator" style="clear: both; text-align: center;">
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">We had a nephrology appointment for Samuel and Lars today.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Lars's portion was very quick. His kidneys still show no sign of Fanconi syndrome, and his growth trajectory has stayed in the 90th percentile. He's gaining on Sam in weight pretty quickly. He was excited to show the doctor the g-tube button I drew on his tummy last night. Early diagnosis is huge! </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Sam's portion was lengthy, to say the least. A lot has happened. Sam got two doses of rituximab, a week apart, the beginning of April. Then we went to Newport Beach, CA for family vacation and the Cystinosis Research Foundation family conference the third week of April. Sam had a cough and runny nose when we drove to California, and seemed to be more tired. We went to Disneyland on that Tuesday, and that totally wore him out by about 3 PM. He refused to walk anymore and slept in his stroller from about 4 PM to 8 PM while Lars continued going on rides. That night he vomited multiple times and had trouble keeping his potassium and citrate down. On Wednesday we slept in and Sam didn't feel well. He rallied for an afternoon at Laguna Beach with his best buddy Henry Sturgis, but afterwards he was too sick to eat dinner with us. We thought that he was just exhausted from a busy vacation with lots of days in the hot sun. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">That night we met up at the Balboa Bay Resort for the CRF welcome dinner. He was surrounded by so many old friends, including Henry and Jackson, that he forgot he was sick and went wild. Friday was the first day of meetings, so we dropped Sam and Lars off at the babysitters, which is Sam's absolute favorite thing (more than Disneyland!). He said he didn't feel well, and instead of joining in on the fun and games, he sat by the television. When we went to pick him up he told us his right wrist was hurting, and he refused to move his right arm. He had pain with walking too, especially on the right side, and had to be carried. He spent Friday night wrapped up in a blanket, sitting in the stroller, instead of playing on the beach. Henry came and checked on him lots of times to see how he was doing. He is such a good friend. When we brought Sam back to the hotel he was in agonizing pain in his right wrist and wouldn't walk because his legs hurt. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">We called our nephrologist back home who thought it sounded like a viral infection. He recommended supportive care. We let him sleep in on Saturday morning, hoping some more rest would help. His wrist was still very painful that morning, and he was acting really sluggish. Ashton called our nephrologist again, and he became more concerned that this was a possible drug reaction. He recommended that we take him to a hospital in California to be seen by a doctor. We knew this carried the risk of him being admitted to the hospital there. Luckily we were at a conference with many doctors, including Dr. Grimm, who used to see Sam in the RP103 trial. Dr. Grimm was very kind to evaluate Samuel. He was concerned that Sam had a reactive arthritis, that could be viral, or it may have something to do with Sam's prednisone taper. He recommended going back up to 30 mg of prednisone and then driving back to Utah to be seen at Primary Children's. We agreed that this was probably the best plan so with very heavy hearts we left the conference early to head home.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Sam threw up a lot on the way home, but eventually it stopped. His wrist stopped hurting too, and suddenly he wanted to eat again. I think lots of prayers were answered that day. We made it back in 10 hours. We went to Primary Children's, and fortunately Sam's nephrologist was there rounding. Sam's potassium was low, but our nephrologist didn't think he needed to be admitted, especially since his wrist was looking better. We had been holding Sam's lisinopril because of dehydration, so the protein in his urine had shot up pretty high again. We went home and hydrated Sam with lots of pedialyte.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">We were lucky Sam didn't have to be hospitalized. We continued him on prednisone 30 mg for a total of 5 days, and then tapered down by 5 mg every couple days. We had to re-live all the tantrums and mood lability again, but his other symptoms improved and he was able to go back to school. We've tapered him down to 5 mg daily right now, and this doesn't make him too cranky.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">At today's visit, Sam's growth has plateaued. We might have to supplement with tube feeds again, but for now we'll keep monitoring. His potassium is still pretty low, so we had to go up on that today. He was on 20 mEq four times a day (a lot!) and now he'll be on 27 mEq four times a day. Dang that Fanconi's syndrome. His bicarbonate and phosphate are normal and his glomerular filtration is good. His albumin has normalized too, which is a good sign. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">So is the rituximab working for his membranous nephropathy? We measured his B-cells before and after starting therapy. We can confidently say that the rituximab has obliterated his B-cells. In studies of adults with membranous nephropathy, once the B-cells are gone, you don't have to continue rituximab infusions, so our doctor has decided we can wait on further treatments. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Whether rituximab will lead to disease remission remains unclear. If Sam continues to have the same level of inflammation in his kidneys and protein in his urine, his kidneys will start to decline, and he would need a kidney transplant in 1-2 years. That's a scary thought, but even more scary is the notion that kidney transplant isn't necessary curative for this condition. If the antibodies are still around, they will attack the donor kidney too. So we really need to get rid of those antibodies.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Dr. Cherqui's strategy to cure cystinosis is to take hematopoietic stem cells from the patient, modify them with gene therapy, and then transplant them back. In this process, the patient's bone marrow has to be eradicated with chemotherapy before the autologous transplant. I've been musing about whether this could cure Sam's membranous nephropathy too. Get rid of the immune cells, including the plasma cells that are making the culprit antibodies, and then transplant back healthy, undifferentiated stem cells, that would grow up to be responsible, kind immune cells, with nothing against Sam's kidneys. I actually found a small series where autologous stem cell transplant was tried in 12 patients with treatment-refractory membranous nephropathy. Patients did have an initial significant reduction in the level of protein in their urine, but it didn't last. The big difference, however, is they did not have bone marrow eradication prior to transplantation, so the bad guy immune cells were still hanging around. It makes me think that Dr. Cherqui's human trials can't come soon enough. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">There was one glimmer of hope today. When Sam was first diagnosed with membranous nephropathy, his albumin/creatinine ratio was over 14,000 (that's crazy high). The lowest we could get it with prednisone and lisinopril was 4800. Today it was actually down to 3600 g. Not a complete response, but maybe the rituximab is working . . . </span><br />
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stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com2tag:blogger.com,1999:blog-590688824130380762.post-63138216151597137752015-04-22T20:01:00.000-07:002015-04-23T19:49:08.170-07:00Day of Hope CRF Family Conference 2015<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhhzTOU2wBDsQOFSXdlkCFbp56ivyqn2wrvY6dny1m3MS5TS45bPfd6Do0gT48kdi0HFz2YfTLGc_ZFDR2hqUpUasmSg7Mrbc0vh-VN-r9RM7tD2CBplRnkUqNnBeAekZzzdJB7fVRHt2w/s1600/DoH15+Logo6.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em; text-align: center;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhhzTOU2wBDsQOFSXdlkCFbp56ivyqn2wrvY6dny1m3MS5TS45bPfd6Do0gT48kdi0HFz2YfTLGc_ZFDR2hqUpUasmSg7Mrbc0vh-VN-r9RM7tD2CBplRnkUqNnBeAekZzzdJB7fVRHt2w/s1600/DoH15+Logo6.jpg" height="384" width="640" /></a><br />
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We just got back from Newport Beach, California, where we attended the Cystinosis Research Foundation's family conference. We look forward to it all year. This year we were really excited to have my parents join us.</div>
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<span style="font-family: 'Trebuchet MS', sans-serif; font-size: large;">The conference kicked off on Thursday with the welcome dinner. It's one of the best nights because we get to see so many friends from around the country (and world!). It's like a big family reunion. Thanks to the internet we can follow along with our many cystinosis family friends, but nothing beats getting together and catching up.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Sam and Lars didn't waste any time getting together with their buddies. Unfortunately they both insisted on bringing their lightsabers (Disneyland souvenirs) with them. Sam found Henry Sturgis and they immediately started having lightsaber duels right in the middle of the crowd. I appointed myself designated babysitter and escorted them, along with Jackson Blum, to the lawn outside where they could be as rowdy as they wanted. It was fun to see all the little kids running around in herds. When we left that night Sam was so sad to be separated from Henry. He cried, "I don't want to be apart from Henry!" all the way to the hotel. We assured him they could have breakfast together the next morning, which they did.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Friday morning started off early with family introductions. There was a record number of families this year! Everyone got up and shared their wishes for themselves and their children. We wrote our wishes on colorful paper birds and put them on a large picture of a tree. I wish for the same thing every year, and that is that Sam and Lars will have long, happy and healthy lives. Ashton wished that some day Sam and Lars would be able to be dads.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Nancy started off the first session by talking about the many milestones accomplished by the Cystinosis Research Foundation so far. I followed her with a talk about the basics and history of cystinosis -- a little primer to provide context for the research talks.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Dr. Paul Grimm talked about the nuances of cysteamine therapy. He talked about both Cystagon and Procysbi, and the proper way to take them. One of the important points he made was the effects of food on the absorption of cysteamine. Many people find if they take it with food, they have fewer side effects. That's because food interferes with absorption of cysteamine, so it's not working as well. Protein and fatty foods are the worst things to take with Cystagon. Procysbi works best if you take it with something acidic, like orange juice. The beads dissolve early if you take it with something with a basic pH, like milk, so you get reduced efficacy. Procysbi should be taken at least 2 hours after eating, and you should wait at least a half hour after taking it before eating again. Dr. Grimm also made the point that the goal is not to get WBC cystine levels all the way to zero. Carriers of the cystinosis gene (like me) don't have cystine levels of zero. If you use too much cysteamine you run the risk of developing copper deficiency, which leads to collagen abnormalities, skin lesions and poor wound healing. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Dr. Mary Leonard, a nephrologist from Stanford, talked about the new study she is doing with Dr. Grimm on bone and muscle health in cystinosis. This is a really important topic that has not received a lot of research attention in the past, especially bone health. People with cystinosis have lots of risk factors for abnormal bone density and structure. They are planning to do a comprehensive evaluation of 30 children and adults with cystinosis using high-resolution quantitative CT scans, DXA scans, and exercise equipment to assess muscle strength. This study will provide background data needed to do future studies on possible interventions like mineral supplementation and hormones. The most important things we can do now for good bone health include adequate nutrition, phosphorus and vitamin D supplementation, and weight-bearing activity.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Dr. Bruce Barshop from UCSD talked about a new white blood cell cystine test he has developed. The old WBC cystine test has a lot of variability because there are two main types of white blood cells: granulocytes and lymphocytes. The granulocytes contain the cystine. The ratio of granulocytes and lymphocytes varies from person to person and day to day. During a viral illness, lymphocytes spike to a higher number, so much less cystine is recovered in the lab test, which can give a falsely low cystine level (a little troubling!). Dr. Barshop has developed a new test using immunomagnetic beads to separate the granulocytes from the lymphocytes, giving a more pure preparation with more reliable cystine levels. With the new test, individual hospital labs won't have to process the blood anymore. This means any lab can send blood in a yellow top tube express overnight to Barshop's lab to be analyzed. This will be a huge blessing to people in smaller towns or rural areas where hospital labs are not trained to process blood for WBC cystine testing. There will also be a new reference range for target cystine levels. Basically 1.7 will become the new 1.0. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">After Dr. Barshop's talk, we had a Q&A panel with representatives from Raptor Pharmaceuticals and Sigma Tau. People were able to voice their concerns about drug access (especially outside the U.S.), cost and insurance coverage, and side effects. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Dr. Sergio Catz from the Scripps Research Institute talked about his lysosome research. Typically we think of cystinosis as a disease of cystine accumulation INSIDE the lysosome. He has found, however, that because another receptor (LAMP-2A) in the lysosome membrane is impaired, there is also accumulation of proteins OUTSIDE the lysosome, and this also leads to cellular dysfunction. He has also found a drug that improves cystine emptying from the lysosome by stabilizing a protein called Rab27, which is expressed at lower levels in cystinosis. This work has been done in cell cultures, so the next step is to test the drug in knockout mice.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Dr. Francesco Emma, all the way from Bambino Gesu Children's Hospital in Rome, Italy, talked about screening existing drug libraries for new molecules for treating cystinosis. His lab looked at 1280 different drugs in cystinosis cells to find molecules that reduce cystine levels and protect the cells from apoptosis (a type of cell death). They found one drug that does both of these things, and it could be a potential new therapy for cystinosis. The good news is it's already approved by the FDA for something else. His lab is testing it now in knockout mice. Hopefully in the next year he will be able to reveal the identity of this exciting mystery drug!</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Next we heard from Dr. Stephanie Cherqui, who gave us an update on her stem cell research. She explained the mechanism of how hematopoietic stem cell transplantation rescues organ function in mice with cystinosis, which I broke down in previous blog posts (<a href="http://littlebravesambo.blogspot.com/2014/10/how-to-cure-cystinosis.html" target="_blank">here</a> and <a href="http://littlebravesambo.blogspot.com/2014/10/dr-cherqui-and-amazing-lysosome.html" target="_blank">here</a>). She gave us progress updates on the safety studies that the FDA requires prior to human trials, and so far, everything has gone smoothly. She predicts that she will be done with the safety studies in 8 months, and then she can go back to the FDA to start the phase I trial. The plan is to recruit two people per year, with a total of 6 people. She has organized the Cystinosis Stem Cell and Gene Therapy Consortium, which is large group of physicians and scientists who will design the trial and evaluate the participants throughout the study. 2016 is going to be a big year!!</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">After Dr. Cherqui, we heard from Dr. Celine Rocca, who works with Dr. Cherqui at UCSD. She presented her research on the effects of HSC transplantation on corneal cystinosis. She showed that after allogeneic HSC transplant, cystinosis knockout mice had significant reduction in cystine crystals, restoration of normal corneal thickness and lower intraocular pressure 12 months later. This is the first time someone has shown that HSC transplantation can treat an inherited corneal disease.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Dr. Jennifer Simpson from UC Irvine spoke about the many ways cystinosis affects the eyes. We usually only think about the corneal crystals, but every compartment of the eye is affected, including the retina, conjunctiva, iris and ciliary bodies. One of the biggest take home message was that we shouldn't blame all eye symptoms on the cystaran eye drops. Dry eyes, red eyes or painful eyes can be signs of other eye diseases, like keratitis and glaucoma. She is working on cystinosis guidelines for ophthalmologists, many of whom have little experience treating ocular cystinosis.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Next Dr. Ghanashyam Acharya, from Baylor College of Medicine, updated everyone on the nanowafer his lab has developed to treat corneal cystinosis. He recently published a paper on the nanowafer technology, which the popular media received with a great deal of excitement (<a href="http://www.npr.org/blogs/health/2015/02/20/387301576/dissolving-contact-lenses-could-make-eye-drops-disappear?utm_campaign=storyshare&utm_source=facebook.com&utm_medium=social&fb_ref=Default" target="_blank">see the NPR article here</a>). The nanowafer is so effective, it may replace eye drops for many diseases. Fortunately Ghanashyam worked with Baylor to give the Cystinosis Research Foundation the license for the nanowafer to treat cystinosis, so the CRF is working on filing with the FDA to start a human trial. The hope is to enroll people in December! </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Next we had the physician/scientist panel. We asked many of the questions that people posted on Facebook. Many people had questions about muscle wasting and what can be done to stop it. Dr. Trauner, a neurologist, noted we don't have an effective treatment for muscle wasting, so further research needs to be done. Levocarnitine, vitamin D, vitamin B complex and CoEnzyme Q10 are all thought to help muscle function, but there isn't any hard evidence. </span><br />
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<span style="font-family: 'Trebuchet MS', sans-serif; font-size: large;">Some people asked when was the best time to start eye drops, and whether waiting till the child is symptomatic was too late. Dr. Simpson said children should be started as soon as they are diagnosed. </span><br />
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<span style="font-family: 'Trebuchet MS', sans-serif; font-size: large;">Several people also had questions regarding male infertility, since boys with cystinosis develop hypogonadism. No one on the panel had much experience in this field, but Dr. Leonard said she would talk with her colleagues in hematology/oncology, since they have a lot of experience with preserving fertility in young children prior to chemotherapy. We need to recruit a reproductive endocrinologist to the CRF family! </span><br />
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<span style="font-family: 'Trebuchet MS', sans-serif; font-size: large;">Someone asked the question about what supplements we need to be careful with, and Dr. Grimm noted that giving someone too much phosphorus at one time can drop the calcium in the blood and cause tetany.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">After the panel, Betty Cabrera, who is working with Stephanie Cherqui on the stem cell trial, spoke to us about the Cure Cystinosis International Registry. It's really important for everyone with cystinosis to register and fill out the survey on CCIR so that scientists will have the baseline information they need to do more research. She noted that it's one of the most important things we can do as a community to help find a cure. Even if you've registered before, it's important to update your information annually. The CRF has recently revamped the survey to include more pertinent questions for the nanowafer and stem cell trials. To register, <a href="https://cystinosis.patientcrossroads.org/" target="_blank">click here</a>. </span></div>
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<span style="font-family: 'Trebuchet MS', sans-serif; font-size: large;">While we were listening to grown-up talks, the kids were back with the babysitters getting royal treatment. They watched movies, played games, did crafts, and ate all the potato chips they could cram in. They received a visit from the "Rad Hatter," a mad scientist, Captain America and a princess named Elsa from some movie I'd never heard of. The kids loved it. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Friday night we had dinner on the beach and lawn. Lars headed straight for the water and spent the night digging holes on the beach. Sam usually does the same, but that night he was feeling sick, so he spent the night wrapped up in a blanket in our stroller. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Nancy and Natalie Stack surprised Dr. Grimm with a short film highlighting his life and dedication to pediatric nephrology and patients with cystinosis. They presented him with a special book of photos and letters from his cystinosis patients. There was ice cream, frozen bananas and those wonderful light-up cotton candy wands. Soon the beach was covered with flashing green, red and blue lights as the kids ran around with their wands. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Unfortunately that was the extent of our participation this year. Sam became too sick that night, and Saturday morning we had to get in the car and rush back to Salt Lake City so he could be seen at Primary Children's. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">We missed the Saturday morning sessions, including the teen and adult panel, which is always one of my favorite parts. We also missed the big Natalie's Wish gala, which really bummed us out. They showed the <a href="http://littlebravesambo.blogspot.com/2015/04/cystinosis-research-foundation-2015.html" target="_blank">new 2015 CRF movie</a>, which featured our family. They raised an incredible $2.3 million dollars that night. My parents were still there and presented the check from our 2014 fundraiser, where we raised over $18,000 for cystinosis research. I was really jealous when I learned my parents got to sit with Ghanashyam at dinner. That dude is my hero. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Only 350 days until next year's conference!</span></div>
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stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com0tag:blogger.com,1999:blog-590688824130380762.post-78697931689918894162015-04-21T14:45:00.000-07:002015-08-09T20:54:06.644-07:00Cystinosis Research Foundation 2015 Movie<iframe allowfullscreen="" frameborder="0" height="281" mozallowfullscreen="" src="https://player.vimeo.com/video/125525130?loop=1&byline=0&portrait=0" webkitallowfullscreen="" width="500"></iframe> <br />
<a href="https://vimeo.com/125525130">CRF 2015</a> from <a href="https://vimeo.com/user35736343">Nancy Stack</a> on <a href="https://vimeo.com/">Vimeo</a>.<br />
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<br />
<span style="font-size: large;">This year the Cystinosis Research Foundation made a short film about our family for the 2015 Natalie's Wish event. The filmographer, Lars Wanberg, spent a week with our family back in January. The film talks about living with cystinosis and the amazing research the CRF is funding to make life better for our boys and every person with cystinosis. Take a look! </span><br />
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<br />mildredhttp://www.blogger.com/profile/02034924909970073272noreply@blogger.com2tag:blogger.com,1999:blog-590688824130380762.post-80291148125037309412015-04-05T20:21:00.000-07:002015-04-05T20:23:00.909-07:00Sam and Buddy<br />
<span style="font-size: large;">Here is a story Sam wrote today. He wanted to play Plants vs. Zombies on the i-Pad for the millionth time, so we told him he needed to write for 30 minutes. This is what he came up with:</span><br />
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<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiv0FI3LU1E1ZT6UEh9UrXReEUkgUAwtsvDVBJt8oo0HlgXnyYOsEv3LXlXBryefLavV4oYoYf5yNUTkLTDJHmSSu0T9i4Izz6-cEEOFtbdMO196TaReBpQTEhLFQPdyPvDrFmeGWuI_l4/s1600/photo+(7).JPG" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiv0FI3LU1E1ZT6UEh9UrXReEUkgUAwtsvDVBJt8oo0HlgXnyYOsEv3LXlXBryefLavV4oYoYf5yNUTkLTDJHmSSu0T9i4Izz6-cEEOFtbdMO196TaReBpQTEhLFQPdyPvDrFmeGWuI_l4/s1600/photo+(7).JPG" height="640" width="478" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><i style="font-size: x-large;">Sam and Buddy</i><span style="font-size: large;"> </span><span style="font-size: large;"><br /><br />Buddy was Sam's dog.</span></td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiszeoyNLU56dezZYaH_Ky540gckdr2COTRE17P967G_l-1O8PWccqVd1DdFFvIM7MDg5HCJ-gXbjN32dT7VXCOmrYgRLj65hvnCf6oR5B7gijIa4vU0s5UybaHLpcTfiTBbogho92BOzs/s1600/photo+(8).JPG" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiszeoyNLU56dezZYaH_Ky540gckdr2COTRE17P967G_l-1O8PWccqVd1DdFFvIM7MDg5HCJ-gXbjN32dT7VXCOmrYgRLj65hvnCf6oR5B7gijIa4vU0s5UybaHLpcTfiTBbogho92BOzs/s1600/photo+(8).JPG" height="640" width="478" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><span style="font-size: large;">Sam loved Buddy. Buddy was a homeless dog.</span></td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhqa0qZm5ZjXC8WfYSKAdWW5wWnYiI47k2xuh-zZeQOdtqDsFLtl_3Bg8O7jXYY8mqElCu83Rr1delgXJB5lq-gqa7J7khM4S3fIANClgk7EDs7rfD-sYPpXvhdgFmN3kOXNF7ihuumTtM/s1600/photo+(6).jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhqa0qZm5ZjXC8WfYSKAdWW5wWnYiI47k2xuh-zZeQOdtqDsFLtl_3Bg8O7jXYY8mqElCu83Rr1delgXJB5lq-gqa7J7khM4S3fIANClgk7EDs7rfD-sYPpXvhdgFmN3kOXNF7ihuumTtM/s1600/photo+(6).jpg" height="640" width="478" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><span style="font-size: large;">He came to me in the woods. I was taking a walk.</span></td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjxlwyR9rvbLtpiFTO3W_7KO_rVGWT6-lQYNoCKcBD8r3FP7x-ndXOLZtALkbb7H3qB0S1CksDb65UW1lKea7KdKqnNRZr_pHDpT5suPEFY_OrrjFTBOmFOpCqD9ic4L7QWzA_HYkckFKg/s1600/photo+(5).jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjxlwyR9rvbLtpiFTO3W_7KO_rVGWT6-lQYNoCKcBD8r3FP7x-ndXOLZtALkbb7H3qB0S1CksDb65UW1lKea7KdKqnNRZr_pHDpT5suPEFY_OrrjFTBOmFOpCqD9ic4L7QWzA_HYkckFKg/s1600/photo+(5).jpg" height="640" width="478" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><span style="font-size: large;">"Do you have a home?" And Buddy said, "Ruff!"</span></td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjiV2hHpvjGKMe8c1I-zTbVnyB2F7nnVrqwGgF0rSMhmhMIBKjFZvcq8BAwLlAK5QRfiN7AoVcyQBZ3Km3IAg3_qYbg4Kd8gg3r0Ndnfi0vT97ZISlUQ-RfnGhTcYO0k35tBjpucfg1adg/s1600/photo+(4).jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjiV2hHpvjGKMe8c1I-zTbVnyB2F7nnVrqwGgF0rSMhmhMIBKjFZvcq8BAwLlAK5QRfiN7AoVcyQBZ3Km3IAg3_qYbg4Kd8gg3r0Ndnfi0vT97ZISlUQ-RfnGhTcYO0k35tBjpucfg1adg/s1600/photo+(4).jpg" height="640" width="478" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><span style="font-size: large;">I knew he did not have a home. I took him home. <br /><br />The End.</span></td></tr>
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<br />stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com0tag:blogger.com,1999:blog-590688824130380762.post-42081461190735176912015-03-31T19:41:00.000-07:002015-03-31T19:48:44.558-07:00Plan B: Rituximab<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiNko9CH5VCcrbTgdnK3cKI0sUkojrxPAuhR1_joclx-43DI53dlHLK8aJbUUs_snS34mOWdjUJyKJ1qq-DnzixEVqa47xCwAwMb3BPqh4bJPlL9isznSNCKcErbaMsndYLvRlWfUlgRp4/s1600/photo+(3).JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em; text-align: center;"><span style="font-family: Trebuchet MS, sans-serif;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiNko9CH5VCcrbTgdnK3cKI0sUkojrxPAuhR1_joclx-43DI53dlHLK8aJbUUs_snS34mOWdjUJyKJ1qq-DnzixEVqa47xCwAwMb3BPqh4bJPlL9isznSNCKcErbaMsndYLvRlWfUlgRp4/s1600/photo+(3).JPG" height="640" width="478" /></span></a><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Today Sam got his first infusion of rituximab. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Let me back up. Our plan was to try high dose prednisone for 3 months to see whether that could shut down the antibody response that is damaging Sam's kidneys. Sam was on 30 mg of prednisone daily. It was terrible. We have so much sympathy now for anyone who has to take prednisone, especially high doses. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">We had heard it could make you ornery, but we still weren't ready for the unpredictable mood swings and tantrums. It was like Mt. Vesuvius every fifteen minutes. Sam is a stubborn kid at baseline, but there was a noticeable change on prednisone. And worst of all, it didn't really work. He still has really high levels of protein in his urine. There was a modest decrease that was most likely due to the ACE inhibitor he started taking, lisinopril. His protein/creatinine ratio dropped from 14 to 5. And his serum albumin came back up into the normal levels. But his kidneys are still inflamed and dumping protein like it's going out of style. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">There were some benefits to prednisone. Sam started eating a lot more. We were able to stop all his night tube feeds, which was nice. His face definitely got chubbier, with little chipmunk cheeks. We'll see if those hang around now that we are tapering off. We are currently down to 10 mg daily, and it will take us another month to get off prednisone completely.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">So prednisone didn't work. That meant we had to move to plan B. Our nephrologist didn't want to use cyclosporine, which is the usual treatment for membranous nephropathy, because it can be toxic to the kidneys. This would be especially risky in a child with cystinosis who is constantly at risk for dehydration. So that left two other options: mycophenolate or rituximab. Our nephrologist went with rituximab.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Rituximab is an antibody against the cells that make antibodies (wrap your head around that). It targets the precursors to B-cells. B-cells are important immune cells that recognize bad guys like bacteria and viruses, and they make antibodies against them. Sometimes they get confused and make antibodies against things in the human body. That's how autoimmune diseases like rheumatoid arthritis and Crohn's disease happen. Rituximab is an effective treatment for autoimmune diseases because it takes out the B-cell precursors. No B-cells, no antibodies. Rituximab was actually originally developed for B-cell lymphomas. In lymphoma the B-cells start proliferating out of control, so rituximab can be given in addition to chemotherapy to get rid of the cancer cells.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Rituximab is expensive, so our nephrologist had to make a special case for Sam to get it. Then Ashton had to call our insurance and Primary Children's a million times to get the pre-authorization processed. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Since rituximab is given through an IV, Sam had to come to the hospital for his infusion. We were admitted to the Rapid Treatment Unit (RTU), which is where he stayed after he got his kidney biopsy. It's like an observation unit for short stays. Since rituximab is an antibody there is always the risk of an allergic reaction. To minimize this risk, Sam got benadryl, tylenol and solumedrol before his infusion. Then they ran the rituximab really, really slow. Luckily Sam didn't have any reactions to it. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Sam was pretty apprehensive about the IV. He brought five of his stuffed animal dogs with him for support. Luckily the IV team got it placed on their first try. Then it was just room service and movie marathon after that. He watched Frozen, Matilda and the Nightmare Before Christmas while chowing down on a cheeseburger and Pringles. We haven't been watching TV at home so this was his opportunity to binge.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">The plan from here is to do an infusion once a week for three more weeks. That will be a full course of treatment, and it should knock his immune system down for three to six months. We'll track the protein in his urine and see if it slows down in the next month. If it doesn't work, I don't know what plan C is. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Rituximab has to work. We'll be praying for that and we appreciate your prayers too.</span><br />
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stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com4tag:blogger.com,1999:blog-590688824130380762.post-45465701261345014582014-12-15T18:27:00.001-08:002014-12-15T18:27:15.496-08:00The Plan<div class="separator" style="clear: both; text-align: center;">
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">On Thursday we met with our nephrologist. He spent about an hour going over his thoughts and what the plan is from here. He is just as baffled by the diagnosis of membranous nephropathy as we are. He sees it in adolescents, but not in kids Sam's age. He is fairly confident it's an autoimmune process in Sam. We are still waiting for the phospholipase A2 antibody test to come back, but he doubts that this is the real problem in Sam. He thinks it's a drug.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">What drug? The one that is supposed to be prolonging Sam's life by helping get cystine out of the lysosomes. Cysteamine, also called Cystagon (the short-acting 6-hour pill that Lars is on) or Procysbi (the long-acting $350,000-a-year drug that Sam is on) has a sulfhydryl group on it. The most common drugs (besides NSAIDs) that have been implicated in membranous nephropathy have a sulfhydryl group, including captopril and penicillamine. Something about the way the sulfhydryl interacts with proteins in the body triggers an immune response that has downstream effects that damage the kidneys. This is all speculation, but it's the best hypothesis our nephrologist has. It's a hypothesis that's impossible to prove, and we can't really take him off the drug anyway.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Everyone with cystinosis takes this drug. Why hasn't anybody else every developed membranous nephropathy? Good question. If you search the published literature for a case of cystinosis with membranous nephropathy, you won't find one. Our nephrologist is going to write a case report about Sam, to get it on the books. Just because it's never been published before, doesn't mean it doesn't happen. Other kids with cystinosis do get protein in their urine. Usually it's during the teen years, when the kidney is progressing toward needing a transplant. At that point, people rarely get biopsies. The doctor just blames it on cystinosis and the patient gets a transplant. A lot of patients don't routinely get their urine checked, either, so if there is protein in the urine, it is not being detected. It would be a really interesting study to collect urine samples from a bunch of cystinosis patients to see what the prevalence of albuminuria in the general cystinosis population is . . . I might have to do that study one day.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Enough of the speculation. What is the plan? Well, since it's an autoimmune disease, our nephrologist wants to start with prednisone. We are going to try three months of high dose prednisone to see if we can shut it all down. </span><span style="font-family: 'Trebuchet MS', sans-serif; font-size: large;"> Prednisone is cheap and it's been around forever. Anyone who has ever taken it will tell you it has side effects. One of the side effects in children is "orneriness." At least we have something to blame when Sam throws a tantrum! Another side effect, and maybe a silver lining, is increased appetite. Sam has only been on the medicine for 4 days, but we can already see this in action. He shovels in the food, and then comes back for seconds and thirds. </span><br />
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<span style="font-family: 'Trebuchet MS', sans-serif; font-size: large;">The other medicine Sam is starting is lisinopril, an ACE inhibitor. This medicine decreases filtration through the kidney, reducing how much protein leaks out. It is a blood pressure medicine, so we are starting on a real small dose to make sure Sam can tolerate it. It can bump the creatinine too, so we have to be really careful when he gets dehydrated. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">We got some more bad news last week as well. Sam's cystine level came back at 1.99. It is supposed to be below 1. His levels have been really hard to control ever since he switched to swallowing pills, and since he started school. It screwed up our whole schedule. We went up on the dose of Procysbi, and we are also stopping night feeds, since the Boost formula negatively affects Procysbi absorption. It's nice for Sam to not have to do night feeds anymore, but we do worry about him getting enough calories. Hopefully starting the prednisone will balance that out.</span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">So that's the plan. Prednisone for 3 months, lisinopril probably indefinitely. We'll be checking labs every 2-4 weeks and hopefully get things under control. If prednisone doesn't work, we'll be moving to the next line, which would probably be rituximab and cellcept. Our nephrologist said he would never use cyclophosphamide or cyclosporine in someone Sam's age (sigh of relief). Too many side effects. He is actually pretty optimistic that we can get the disease into remission, which is reassuring. We'll just have to wait and see. </span></div>
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Thanks for all your prayers and kind words of support. They mean a lot. </span></div>
stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com0tag:blogger.com,1999:blog-590688824130380762.post-61809349954154936102014-12-05T08:08:00.000-08:002014-12-05T08:08:09.195-08:00Membranous Nephropathy<div class="separator" style="clear: both; text-align: center;">
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">We got the preliminary results back on Sam's kidney biopsy from the nurse practitioner. We still haven't heard back from our nephrologist (!!!), so we have a lot of unanswered questions. <b> It was not what we were expecting at all.</b> The most common cause of nephrotic range proteinuria in kids is minimal change disease, something that responds pretty well to a course of steroids. That would've been "good" news. The bad news we predicted was that the biopsy would show scarring from cystinosis, something irreversible and an indicator of progressive kidney dysfunction, likely requiring transplant earlier in life. <b>What we found was a whole new version of bad news</b>. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">The pathologist found <b>membranous nephropathy</b>, a microscopic pattern that makes doctors cringe with painful memories of cramming for exams. Membranous nephropathy is certainly on the list of things that cause protein in the urine, but it wasn't on our list. It's fairly uncommon in adults, and from what I've read, it's pretty rare in children. So how about that? Sam has two rare diseases. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">What causes membranous nephropathy? The most common cause is "idiopathic," meaning doctors don't know exactly. Other causes include lupus, diabetes, certain drugs including gold salts and NSAIDs, hepatitis B, and some cancers. But what causes it in kids? The most common cause in children is the autoimmune variety. That means Sam's body has probably made antibodies against something in his kidneys. A possible target is the phospholipase A2 receptor. Sam is getting tested for that antibody today.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Autoimmune diseases are treated with immunosuppressant medications. Membranous nephropathy is treated with cyclophosphamide, a chemotherapy drug, or tacrolimus, cyclosporine or mycophenolate, all drugs commonly used in organ transplants. We will also most likely have to use an ACE inhibitor too, to help reduce protein leakage. New medications with new side effects, some of which are pretty terrible. With therapy, about half of cases will go into remission. About a third of cases go into remission and then relapse later. The rest are progressive, leading to end-stage renal disease.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">So you can see how this is bad news. Before we were "just" battling a rare genetic disease, with a glimmer of hope that it could be cured with stem cell transplant. Worse case scenario before was that Sam would still have to get a kidney transplant, but we were going to beat the odds. Now he has something else attacking his kidneys -- his own immune system. Now if he gets a kidney transplant, there's a chance the antibodies will attack the new kidney too. </span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">We were finally feeling adjusted to our life with cystinosis. This is the kind of situation that makes you look up into the heavens and ask, "Anything else?" We have always tried to be optimistic, but this feels a little like running into a brick wall.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">The silver lining is that there wasn't a lot of scarring. There was some "focal" glomerulosclerosis, but not widespread. And there weren't a lot of cystine crystals, either. So I guess we can feel okay about the efficacy of Procysbi. We had been worried about that, blaming ourselves for getting Sam in the trial when he was so young, before it had been tested in children. At least we can put that to rest.</span><br />
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<span style="font-family: Trebuchet MS, sans-serif; font-size: large;">Sam is a fighter. Literally, you should see him beat up Lars. This is the biggest curveball yet in our journey with chronic disease. If there's one thing I have faith in, it's that Sam is not going to let some histologic mouthful stop him from living life to its fullest. He can still become a ninja, doctor, pilot, spy, or whatever else he comes up with next. </span>stevesiehttp://www.blogger.com/profile/14265495084137238383noreply@blogger.com8