Wednesday, April 30, 2014

THANK YOU to... Hip & Humble

Dear Friends and Family, 
The upcoming silent auction for Sam's Hope for a Cure is going to be AWESOME because Hip & Humble just donated a $50 gift card!  My mother-in-law, Leslie, introduced me to Hip & Humble shortly after Stephen and I were married.  I LOVE IT!  I feel creatively inspired every time I enter the store.  The cute alphabet cards from Sam and Lars' room are from here.  Check out their stores.

Salt Lake City, Utah

1043 East 900 South

Bountiful, Utah

559 West 2600 South

Sandy, Utah

676 East Union Square (9400 South)

We're on Apartment Therapy! Check it out.

Wednesday, April 23, 2014

Vitamin D and Muscle Wasting

Dr. Robert Mak, a pediatric nephrologist, gave a talk at the 2014 CRF family conference about the effects of Vitamin D on muscle wasting in cystinosis.  His talk generated a lot of excitement and interest, so I thought it would be worthwhile to break it down here.

Muscle wasting is one of the major complications of cystinosis, and it is typically seen later in life, in the second and third decade.  Cystine accumulation damages muscle cells.  The muscles predominantly affected are swallowing and limb muscles.  Many patients with cystinosis have trouble swallowing, especially as they get older, and the deterioration of these muscles can lead to aspiration of food and saliva into the lungs, which can cause serious complications, even death.  Wasting of the limb muscles can cause weakness in grip strength and affect dexterity, as well as exercise endurance.

Currently, there are no great therapies for muscle wasting.  Cysteamine depletes the cystine in the muscle tissue, but even patients taking cysteamine eventually develop muscle wasting.  Many cystinosis patients take carnitine supplements since this compound is wasted in the urine.  Carnitine is required for muscles to break down fat into energy, and carnitine deficiency leads to accumulation of fat in muscle tissue.  Giving patients carnitine supplements will normalize blood and muscle levels of carnitine, and it reduces accumulation of fat in muscle tissue, but no studies have been done to assess whether carnitine replacement results in higher muscle mass or better growth in the long term.   Dr. Doris Trauner, a neurologist, mentioned in her remarks at the CRF conference that other proposed treatments for muscle wasting include coenzyme Q and the different B vitamins. 

Dr. Mak has been studying the effect of vitamin D on muscle wasting using a mouse model for cystinosis.  In the mouse model, the gene that codes for the cystinosin protein has been "knocked out," so the mouse no longer makes the protein.  This effectively creates a mouse with cystinosis, and it is a good surrogate for testing different therapies, like vitamin D. 

Normally we make vitamin D in our skin, with exposure to sunlight.  We can also get vitamin D from fortified foods, or from supplements.  If the supplement is from a plant, it's called ergocalciferol, or D2.  If it's from animals or our skin, it is called cholecalciferol, or D3.  Whether we make it in our skin or eat a supplement, the vitamin D is modified by the liver to make 25-Vitamin D.  This form of vitamin D is then modified again by the kidneys, to 1,25-Vitamin D, which is the active form.  This form is also called calcitriol, and it is required to maintain calcium and phosphate levels in the blood and promote bone growth and remodeling.  1,25-Vitamin D increases absorption of calcium and phosphate in the intestines, both of which are needed for bone mineralization.  Patients with renal failure often have to take calcitriol because their kidneys can't make the active form anymore.

Dr. Mak pointed out three reasons cystinosis patients have low vitamin D: they lose it in their urine, they spend less time outside in the sun because of photophobia, and they develop chronic kidney disease. Doctors have always known that it is important to treat vitamin D deficiency in cystinosis patients, since vitamin D deficiency leads to rickets (in addition to the phosphorous wasting seen in Fanconi syndrome).  Low vitamin D levels may also be bad for the muscles.

Dr. Mak has shown that cystinosis mice with vitamin D deficiency have smaller muscle fibers, weaker grip strength, poor balance, and energy wasting.  He has also shown that vitamin D deficiency leads to genes being turned on that break down protein, which leads to muscle wasting.  He treated cystinosis mice with 25-Vitamin D (the kind your liver makes) and 1,25-Vitamin D (the active form that your kidneys make).  He found that in the mice treated with 25-Vitamin D, there was restoration of muscle mass, muscle fiber size, grip strength and balance, more than in the mice treated with 1,25-Vitamin D.

Remember that 25-Vitamin D is just the regular over-the-counter supplement after it is modified by the liver.  This is the form that the muscle uses, because the muscle has its own enzyme to activate it.  So while 1,25 Vitamin D (calcitriol) is crucial for bone health, it does not appear to be as important for muscle health. 

So what is the take home message?  Vitamin D deficiency is bad for muscles, so taking a vitamin D supplement is a good idea if you have low levels, and it may even help prevent muscle wasting.  This doesn't mean you should just start taking big doses of vitamin D, however, because you can theoretically get vitamin D toxicity.  Dr. Mak and Dr. Grimm said that if your doctor hasn't done it already, get your vitamin D levels checked, and if you are deficient, then take a supplement.

We built Sam and Lars a rock climbing wall in their bedroom to help them with limb muscle strengthening, especially arms and hands.  We have absolutely no evidence that it will make a difference in the long run, but it seems like a good idea, and they have a lot of fun with it! 


Wednesday, April 9, 2014

Ghanshyam and the Magical Cysteamine Patch

The most exciting surprise at the Cystinosis Research Foundation family conference this past weekend was when Kevin Partington pulled up his sleeve to reveal a patch on his arm.  He wasn't quitting smoking or going through menopause.  The patch was a novel cysteamine delivery system developed by Dr. Ghanashyam Acharya. 

Dr. Acharya was introduced to the cystinosis community at the 2013 conference, and he made quite a splash with his energy, enthusiasm and unbridled optimism.  He was recruited to the fold by Dr. Jennifer Simpson to develop a better way to treat corneal cystinosis.  Together they came up with a nanowafer that is placed on the surface of the eye like a contact lens, which releases cysteamine gradually for a day, and maybe up to a week at a time.  Currently the only treatment for corneal cystinosis is Cystaran eye drops, which must be applied every waking hour to eliminate corneal crystals.   Dr. Simpson has since used confocal microscopy and a mouse model of cystinosis to show that the wafer is much more effective at reducing corneal crystals than eye drops.  Hopefully we'll have a clinical trial in the near future!

Something else Dr. Acharya talked about at that 2013 conference was his previous experience using nanotechnology and microparticles to create longer acting drug formulations of felodipine, risperidone, progesterone, and paclitaxel.  The new formulation of the antipsychotic risperidone can be given as an injection at 6 week intervals, which has obvious benefits for people with schizophrenia and problems with medication compliance.  My mind started racing as I imagined what a long acting version of cysteamine could mean for patients with cystinosis.  We love Procysbi, which is every 12 hours, but I still worry about the fluctuations in Sam's cystine levels.  I was picturing something like a depot shot, given maybe once a week, or even once a day.  I talked with other families that morning who had come to the same conclusion.  I was so excited about the idea that I submitted a question on an index card at the Q&A physician panel, addressed to Dr. Acharya, to see whether he believed it were possible to create a depot shot for cysteamine.  His response was simple and confident.  "Yes, I can do that."

But there were naysayers on the panel, and their reasoning made sense.  They said things like, "The amount of medication you need to deliver would make it impossible.  We're talking about grams of cysteamine!"  I think a lot of people felt deflated by these remarks, including myself.  But Ghanshyam insisted he thought it could be done.  The gauntlet had been thrown down, and the wheels in Ghanshyam's head started moving.

Fast-forward one year to the 2014 Day of Hope Conference.  Ghanshyam brought a prototype patch with him, and after his talk updating us on the cysteamine nanowafer for the eyes, he gave us the quick run-down on how he developed it.  He said he went back to Baylor after the conference and rounded up his four post-docs, put their other research on hold, and brainstormed for a solution.  The main problem was the amount of drug to be delivered.  Most skin patches, like fentanyl, estrogen and nicotine patches have very small amounts of drug (like micrograms), and this allows the drug to passively diffuse through the skin and into the bloodstream.  A cysteamine patch would require an active pumping mechanism, and something like this has never been done before.

The physics was way over my head, but basically Ghanshyam invented a completely new model with multiple layers that are able to convert the mechanical energy of body movement into electrical energy that could pump the cysteamine into the skin.  He calls it something like a quantum kinetic transdermal patch.  He thinks he can get 500 mg, or half a gram, of cysteamine into the patch, and his goal would be to have it last 3 days.  The advantages of the patch are obvious.  Medication compliance would go to 100%, and the peaks and troughs associated with every 6 hour dosing would be flattened into a continuous basal rate of drug delivery.  This would likely mean that less cysteamine would be needed per patient, and side effects would probably be minimal.  The patch may also solve the problem that Dr. Dohill has pointed out, where he found that 2 hours after drug ingestion, cysteamine cannot be detected in tissue.  The patch could mean stable cysteamine levels all the time, with better predictability of cystine levels in cells.

I was able to talk with Ghanshyam on Friday night at the dinner, and he told me how he loved to solve seemingly impossible problems.  He said you can never take no for an answer.  He told me he used to work at NASA, and there he learned the motto "failure is not an option."  He said he's not in this business for the money.  He just wants to find solutions, and to make life better for children and adults with cystinosis.  I propose we clone one hundred more Ghanshyams.

On Saturday when families were sharing the challenges and silver linings of living with cystinosis, Ghanshyam's wife took the microphone for a moment.  They were just married in the last year.  She said that right after they were married, Ghanshyam would wake up at 2 o'clock in the morning and tell her he needed to go to the lab.  She said she thought he was crazy, but she said that after coming to the Day of Hope conference and meeting the cystinosis families, she understands why he works tirelessly and with such urgency.  She said she would never question his late night lab antics again, to much applause and laughter.    

Ashton and I joked at the conference that if we ever had another son, we were going to name him Ghanshyam.  At the time it was an easy declaration to make, because after having a second child diagnosed with cystinosis, we have felt like we are probably done having kids.  But with the patch and a possible cure in the pipeline, taking another roll at the dice might be in the future.   

Tuesday, April 8, 2014

2014 Cystinosis Research Foundation Movie

Check out this awesome movie from the CRF.  It talks about the newest research and treatment goals, and features Samuel and Lars!

Monday, April 7, 2014

Cystinosis Research Foundation 2014 Day of Hope

Sam and Henry

We just returned last night from the CRF Day of Hope family conference in Newport Beach, California.  This was our second time as a whole family, and it is the highlight of the year, even bigger than Christmas!  Nancy and Geoff Stack go all out to make the families feel welcome, comfortable, educated, and, most importantly, full of hope that life for people with cystinosis will get better and better.  There were 40 families that attended this year, and it was like going to a big family reunion.

We chose to drive again because it's just easier for us to deal with screaming children in our own car than on a crowded airplane.  It's also nice to have constant access to snacks (Lars's favorite word) and have room to bring blankets and sleeping pads and basically anything else we feel like cramming in our car.  The boys made sure to bring their new stuffed animal dogs they got from Ashton's grandma, Jackie.

The conference kicked off with dinner at the Balboa Bay Resort.  It's a fantastic evening where we see old friends and meet new ones while our children run wild (despite parental instructions).  It's amazing to watch the kids together.  Sam reconnected with Henry Sturgis immediately, and also had fun playing with Jackson Blum and Andrew Cunningham and chasing Tina Flerchinger.  We were all pretty worn out that night from traveling, and went to bed right after medicine time.

Sam and his buddies Henry Sturgis, Andrew Cunningham and Jackson Blum.

Friday morning we had breakfast and then dropped the kids off with the babysitters.  This is one of the things we love the most.  Lars was in heaven with the huge snack table and unlimited opportunities to scribble with markers.  Sam loved playing with all his buddies and seeing Spiderman. 
The conference started with all the families circling up, and we each got to get up and share what our wishes are for our loved ones with cystinosis.  Ashton wished that Sam would be able to fulfill all his dreams, and that Lars would never need a kidney transplant.  I wished that they would both have long and happy lives.  Sam wished that Lars would become a Greek soldier, and wished for himself to become a spy.  We put our wishes on paper cutouts shaped like flowers and put them all up on a large tree representing our cystinosis family.  It was really a beautiful symbol.  The best moment of the morning was when Kevin Partington lifted up his sleeve to show off the prototype patch that Ghanashyam Acharya has been working on for the last year as a better way to deliver cysteamine.  Ashton and I both started crying when we saw that.  There were a lot of tears shed in general that morning. 

The rest of Friday we went to talks by the different researchers and physicians in the cystinosis community.  Dr. Grimm gave a fantastic lecture on living with Fanconi syndrome, and Dr. Mak got everyone excited about the potential benefits of Vitamin D on muscle wasting.  Dr. Dohil described the research related to GI issues in cystinosis, including the development of Proscysbi.  Dr. Sergio Catz talked about a novel mechanism for improving removal of cystine from lysosomes, which involves trafficking by a protein called Rab27.  He's looking for an existing drug that would induce Rab expression, forcing lysosomes to fuse with the cell membrane and dump their contents.  It sounds like a pretty cool adjunctive therapy to enhance the effects of cysteamine.

Dr. Cherqui gave us an update on her progress with the autologous stem cell transplant project, and said she hopes to have a clinical trial in 2-3 years.  Dr. Jennifer Simpson and Dr. Ghanashyam Acharya gave updates on their nanowafer delivery system for corneal cystinosis, which should be in a clinical trial soon.  Then Dr. Acharya spent just a few minutes talking about the development of the patch, which is very exciting.  All of these talks were followed by a question and answer session with the physicians and researchers, and then a brainstorming session for parents to discuss solutions to common problems like eating, bedwetting, etc.

Spiderman and Cinderella came to visit.  Sam was probably more interested in Cinderella.
Friday night was definitely Sam's favorite.  We ate dinner on the private lawn/beach of the Balboa Bay Resort.  Sam brought shovels and buckets and spent most of the evening digging and getting drenched.  We finally had to drag him away from the water and change his entire outfit because he was completely soaked.  There was cotton candy for the kids on plastic light-up sticks, which was a huge hit.  The Stack's think of everything!  Sam wielded his stick like a lightsaber, and instigated a war with the girls on the beach.  He said Gabbie Strauss was the captain of the girls.  It was pretty epic.  We also sang happy birthday to Mack Maxwell, who turned 50 years old that night!

Saturday we resumed meetings and heard from Dr. Grimm again about kidney transplants, which was a very helpful and educational talk.  Who knew that cats were so dangerous for transplant patients?!  It's a good thing we're a dog family.   And it turns out cystinosis patients keep their transplants longer, probably because of the anti-scarring properties of cysteamine use.  We also heard from Dr. Doris Trauner on neurologic issues in cystinosis, and Dr. Angela Ballantyne, who talked about practical ways of dealing with neurologic, behavioral and educational issues, as well as quality of life.

Then we heard from the real giants, the adult/teen panel.  Bailey, Joe, Jennifer, Shannon Keizer, Natalie, Tom, Mack, Bryan and Shannon Paju all shared inspiring insights about growing up, going to school, working, and living with cystinosis.  Some of the most interesting confessions surrounded medication compliance, which underscores the importance of better drugs like Procysbi to improve medical adherence.  We ended the session with another family discussion where people shared the challenges and silver linings of their journeys with cystinosis.  There was a lot more happy crying and hope.  We started talking about the "Power of Awesome," when Erin Little surprised Nancy Stack with a beautiful quilt of the Day of Hope Tree, with pieces of fabric sent in by families from around the world.  That was pretty cool.

Saturday night was the big Natalie's Wish event, which is always incredible.  We got to present our check from Sam's Hope for a Cure, which included money raised in 2012 with our first letter campaign fundraiser, as well as the money raised in 2013 by Mary Ann Franson with her garage sale, totaling $15,560.  We were so impressed by how much other families, like the Sturgis, Flerchinger, Cunningham and Partington families brought in -- over $600,000 combined!  We had an excellent dinner and got to sit with the Smethhurst family from Logan and the Head family from the Seattle area.  A big highlight was seeing the new 2014 movie, which featured Hadley Alexander and her family.  We were surprised and delighted to see some clips of Sam and Lars in the video as well (even if it included a traumatic blood draw!)  Altogether the event raised almost $2.3 million for cystinosis research, and thanks to the generosity of the Stack family, every single dollar will go to research.

It was hard to leave.  That night Sam said, "I want to go to the babysitters tomorrow so I can play with my friends.  I don't want to go home."  We spent the 11 hour drive home yesterday brainstorming on ways we can raise more money and help the cystinosis community.  We are definitely counting down the days until next year.