At the Top of Sam's Wish List

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.

We can't wait to be outside all day long.

Cystinosis Research Foundation Day of Hope 2019

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.

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.

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.

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.

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.

Next, we heard from Dr. Julian Midgley, from Alberta Children’s Hospital in Calgary, Canada.  He talked about the important and complex process of transitioning from pediatric to adult care.  As a pediatric nephrologist, he primarily cares for pediatric patients, but he has continued to follow many adults with cystinosis as well.  He recommended starting early and planning ahead.  Don't wait until the child's 18th birthday.  He noted that when cystinosis patients are young they get excellent care because their parents control everything.  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. 

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.  

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 (link here).  For adults, the best way to calculate GFR is the CKD-Epi calculator (link here).  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.  

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. 

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.  

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" (Amazon link here) which includes coenzyme Q10, levocarnitine and B vitamins.

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.  

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. 

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.  

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 stress, improved LAMP2A distribution and increased megalin expression. 

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.

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.

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.  

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.

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.  

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.  

After Dr. Grimm spoke, we heard from Dr. Benjamin Freedman from University of Washington in Seattle. 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.

Next we heard from Dr. Paul Goodyer about a possible new treatment for people with nonsense mutations. 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. 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.

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. 

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. 

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. 

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!

CRF Day of Hope 2018

This year’s Day of Hope Family Conference was an enormous success.  We had 61 families from all over the world attend this year.  There were families from Australia, Sweden, Norway, Ireland and Canada.  We were excited to welcome 16 new families, ranging from newly diagnosed infants to adults. 

On Thursday night we all got together for introductions.  We all shared a little bit about ourselves, as well as our wishes and hopes.  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.  After introductions we had delicious Mexican food, something I’ve come to look forward to every year.  Our boys chowed down on chicken quesadillas while their friend, Henry Sturgis, ate his weight in chocolate-covered churros.  It was the perfect venue for catching up and getting to know the new families.

On Friday morning we got started bright and early.  Nancy Stack updated us on the amazing progress of the Cystinosis Research Foundation.  Altogether the foundation has raised over $40 million for cystinosis research since its inception in 2003, funding 164 studies in 12 different countries.  It’s pretty remarkable that such a vibrant research community has sprung up around such a rare disease.  After Nancy spoke it was my privilege to go over the basics of cystinosis at the cellular and organ levels.  

Dr. Paul Grimm from Stanford spoke about the genetics of cystinosis.  There are over 100 different mutations identified in cystinosis.  The most common is the 57kb mutation, which affects 50-75% of people of Northern European descent.  What mutations you have determines a lot about how cystinosis manifests.  Some people have very severe Fanconi syndrome, while others have very severe corneal disease.  Some people don’t sweat or tolerate heat very well.  If you have the 57kb mutation, you also have a mutation in the receptor that detects heat from hot chili peppers.  This endows you with the ability to eat very spicy foods. 

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.  It will be administered as an injection, given 2-3 times a week, and may eliminate the need for cysteamine therapy.  If you have the nonsense mutation, you should check it out!  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.  If you would like to get your genetics done, there are companies like www.invitae.com that charge about $200 to run your mutation.  They will even work with your insurance company to try to get it covered.

Dr. Ranjan Dohil from UC San Diego spoke about the gastrointestinal effects of cystinosis.  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.  He also talked about the research that led to delayed-release cysteamine, or Procysbi.  He emphasized that fatty foods significantly decrease absorption of Procysbi, which is one of the reasons it’s important to fast before and after.  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.  Some people may need to wait longer than 30 minutes before eating, if they have delayed gastric emptying.  Everyone’s dose will have to be titrated individually.

Dr. Robert Mak from UC San Diego shared his research on muscle disease in cystinosis.  He has discovered an inflammation pathway that appears to be implicated in muscle wasting and bone disease in cystinosis.  He has found two drugs that block this pathway.  In cystinosis knockout mice, these drugs improve bone and muscle mass dramatically.  He is hopeful to move forward on a clinical trial in humans.

Dr. Kathleen Rickert was a welcome new face this year.  She is an orthopedic surgeon from UC San Diego.  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.  She reviewed the common bone complications in cystinosis, including bowleggedness and knock-knees, and the different medical and surgical ways to manage them.  She recommended getting X-rays periodically to monitor progression of the deformities.  I look forward to hearing again from her in the future.

Rachel Duong from Massachusetts General Hospital shared results from a study by Dr. Florian Eichler on muscle complications in adults with cystinosis.  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.  They found that 14 out of 20 patients reported symptoms of weakness, while 17 patient demonstrated weakness on exam.  They also found that while 12 out of 20 expressed having trouble swallowing, only 6 actually showed evidence of abnormal swallowing on video fluoroscopy.  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.

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.  In his unique practice, he is actually allowed to see both children and adults with cystinosis.  He recommended starting early and planning ahead; don’t till the child’s 18^th birthday.  It will be different for each child and each family, and should be tailored to the patient’s needs. 

Dr. Morgan Fedorchak from University of Pittsburgh spoke to us on a new controlled-release eye drop she is developing.  She uses 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 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.  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.

Dr. Sergio Catz from Scripps Research Institute 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 looking at the kidneys and eyes.  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.  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.

After Dr. Catz, we heard from Dr. Stephanie Cherqui on the upcoming Phase 1-2 clinical trial for autologous hematopoietic stem cell transplant.  She is hoping to submit the IND application to the FDA this summer, and recruit the first patients this year.  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.  They do not have to commit at that point.  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.  Once this process is complete, the patient returns to San Diego to get the transplant.  This consist of single agent chemotherapy (busulfan) to make room in the bone marrow.  Then the modified stem cells are infused back into the patient.  The following month is the riskiest part, as the chemotherapy wipes out your immune system and makes you susceptible to infections.  The patient will have to remain in the hospital for one month until the bone marrow recovers.  After that they will remain in San Diego for two additional months, with weekly check ups.  Then they can go home, but will return every 6 months for 2 years to be evaluated.  If things go well for the first four patients, then the hope would be to do it in adolescents, over 14 years old.  I’m very hopeful the trial can start this year.  Cross your fingers!

Dr. Bruce Barshop spoke about the new granulocyte cystine test.  He showed data demonstrating that overall the newer test has much less variability than the mixed leukocyte test.  The goal for the granulocyte cystine test is less than 1.9.  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.  He unveiled a new shipping kit that will be available soon through Horizon, which will hopefully make the packaging and shipping process much easier.  If you’d like a kit, contact your Horizon representative.

Next we heard from Dr. Patrice Rioux and Dr. Vince Stanton from Massachusetts.  They have formed a company, Thiogenesis Therapeutics, and are working on developing a better form of cysteamine.  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.  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.  They are hoping to move forward with a study, possibly in Australia, to test toxicity in humans.

After a long day of talks we were ready to get outside and have dinner.  The CRF arranged for buses to transport us to the Back Bay park and beach, where we enjoyed a fabulous barbecue feast.  My kids were super excited for the return of the light up cotton candy wands.  After gorging themselves on macaroni and cheese and brisket, they ran down to the beach to start a lightsaber battle.  I had to sample every dessert, which included fresh donuts and made-to-order ice cream cookie sandwiches.  I think I gained 10 pounds.  It was a beautiful setting and a great night to relax. 

On Saturday we heard first from Dr. Mary Leonard, from Stanford.  She and Dr. Grimm did a study looking at bone health in children and adults with cystinosis.  They did a number of tests, including strength testing, DEXA and high resolution peripheral quantitative computed tomography to analyze the muscles and bones.  They found that kids with cystinosis have 32% lower leg strength than healthy controls, and adults have 35% lower strength.  Muscle force was 25% lower in kids with cystinosis, and 13% lower in adults.  The cortical bone was thinner and had lower surface area, and had a 19% lower failure load.  Amount and thickness of spongy bone was lower as well. 

Next Dr. Paul Grimm spoke again, this time about juggling the many aspects of cystinosis care, especially in younger children.  He talked about the importance of regular dosing of supplements for Fanconi syndrome, especially phosphorus, potassium and bicarbonate/citrate.  He also talked about important medication interactions.  Calcium should not be given with phosphorus (neither will get absorbed).  Procysbi should not be given with bicarbonate (the high pH will dissolve the beads prematurely).  Citrate and bicarbonate should not be combined (it causes a fizzy chemical reaction, which is a good recipe for burping).  He talked about indomethacin, and using it to reduce fluid and electrolyte losses. 

The next talk was from Dr. Doris Trauner from UCSD.  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.  The majority of adults tested had sleep apnea, half of which had moderate to severe sleep apnea.  This was previously undiagnosed, which suggests that all adults would benefit from being screened.  She is still actively recruiting patients to undergo overnight sleep studies. 

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.  For me it was very eye-opening to hear these young kids talk openly about their challenges.  It was also cool to see how much they support each other.  I hope we can have another session next year.

After the last session we had a question and answer panel with all our researchers and physicians.  Following that we had a question and answer panel with our adults with cystinosis.  They talked about how they had overcome many of the challenges of cystinosis and living with a chronic illness.  They talked about working, staying active, being compliant with medications, and how to live a full life.  Every year I hear from them I am inspired by their courage and hope.

Saturday night we reconvened for the Natalie’s Wish gala.  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.  We had 25 families present checks to the CRF this year, raising $668,000.  Altogether the CRF raised an incredible $3.5 million.  The best part is that all that money will go directly to research.  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.  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!

Thank you

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. 

Visit Instagram @samshopeforacure for details and to bid on Sept. 8th from 9am - Sept. 9 at 9pm.

Missy Wallace Art - several butterfly prints

Copper Fox Lettering - hand lettered quotes

Banbury Cross - cake

Arctic Circle - $50 gift card

The Dodo Restaurant - 2 $20 gift cards

Boondock's - 2 adult day passes

Porcupine Pub & Grille - 2 $20 gift cards

Rio Grande Cafe - 2 $20 gift cards

Cactus & Tropicals - $50 gift card

Stephanie Ransom - 4 pillow cases

Alpha Smoot - Framed photograph

Sonnet James - $150 gift card

Pop Chart Lab - 100 Essential Novels Scratch-Off Chart

Madsen Cycles - $400 gift card for a full price item

Courtney Bodily Photography - Family photo session

Kimi's Chop and Oyster House - $50 gift cards

Adobe - 1 year photoshop prescription 

Dan Ransom - Canyoneering photograph on canvas

Cous Cous Grill - $25 gift cards

Andrea Aiko Tingey - Foot Zone

Buffalo Wild Wings - Sauces

The School of Dance - 1 month of dance classes (1hr/wk), Sweatshirt, water bottle, dance bag

Hale Center Theater (West Valley) - Tickets to Aida

Epic Inc. - Four prints

Hale Center Theater Orem - Tickets to a show

Gathre - changing mats

Elase - Glycolic peel

Altra Running - several gift cards

Ruth's Chris - gift cards

Cerulean Studios - temple giclee 

Cinemark - 2 tickets

Piper & Scoot - Dress

Lula Roe by Tiffany Opthof - Leggings

Mary Ann Franson - Tuacahn tickets to Mamma Mia

Zach Proctor - Mother and child art piece

Luscious Lips by Whitney - Lip starter kit

Tsunami Restaurant - $75 gift card

Krissi Cook Films - photography session

The Front - 10 climbing passes

Erin Wilson Design - custom baby stats art piece 

Maryn Tan - family photoshoot

Kim Holmes- dental basket

MORE TO COME!