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.