Thursday, April 6, 2017

CRF Day of Hope 2017

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!

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.

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.

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.

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.

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.

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.

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.

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.

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!  

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. 

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!  

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!

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).  

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. 

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 :) 

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. 

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. 

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.  

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.  

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.

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. 

Now only 365 days till the next conference!  We're already counting down the days . . .   


Monday, April 11, 2016

CRF Day of Hope 2016

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!

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. 

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. 

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. 

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 Building Resilience in Children and Teens: Giving Kids Roots and Wings by Kenneth Ginsburg. 

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.  

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 previous blog post.  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.  

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.  

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.  

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. 

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.

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.

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 CCIR website. 

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. 

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. 

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 . . . 

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. 

Dr. Stephanie Cherqui gave an inspiring talk about the potential for stem cell transplantation to cure cystinosis (see my old blog post here).  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!

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, check out my old blog post. 

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.

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, check out my old blog post.     

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. 

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.  

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!  

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.       

Friday, September 25, 2015

We Were on the News!

You've probably already seen this, but in case you haven't, check out the story that Heather Simonsen from KSL 5 did on our family!

Monday, September 14, 2015

Freshly Picked

When I reached out to Freshly Picked 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.
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.   

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

Pineapple - Picnic Pack Limited Edition MoccasinsHeirloom in Blush and Gold - FP Signature MoccasinsBeehive State - Utah Collection Moccasins

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 to find the perfect moccasins for your little one.

Some of our 2015 Sponsors

Thursday, August 27, 2015

Monday, August 17, 2015

Sam and Lars CRF 2015 Outtakes

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!

Wednesday, July 22, 2015

a new start

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.  

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!

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.   

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.

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.

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.  

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.  

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.  

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.  

Hopefully things will start turning around soon, but at least Sam has been feeling better. 


Friday, May 1, 2015

Is Rituximab Working?

We had a nephrology appointment for Samuel and Lars today.

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! 

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.

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.     

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.

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.

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.

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.

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.

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.

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.

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 . . .    

Wednesday, April 22, 2015

Day of Hope CRF Family Conference 2015

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.

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.

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.

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.

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.

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.  

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.

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.  

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.  

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.

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!

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 (here and here).  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!!

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.

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.

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 (see the NPR article here).  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! 

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. 

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.  

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! 

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.

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, click here.        
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. 

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. 

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.  

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.  

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 new 2015 CRF movie, 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.  

Only 350 days until next year's conference!

Tuesday, April 21, 2015

Cystinosis Research Foundation 2015 Movie

CRF 2015 from Nancy Stack on Vimeo.

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!  

Sunday, April 5, 2015

Sam and Buddy

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:

Sam and Buddy  

Buddy was Sam's dog.
Sam loved Buddy.  Buddy was a homeless dog.
He came to me in the woods.  I was taking a walk.

"Do you have a home?" And Buddy said, "Ruff!"

I knew he did not have a home.  I took him home.

The End.

Tuesday, March 31, 2015

Plan B: Rituximab

Today Sam got his first infusion of rituximab.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Rituximab has to work.  We'll be praying for that and we appreciate your prayers too.