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.

http://www.apartmenttherapy.com/sam-lars-happy-handmedown-room-my-room-202867

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! 





 

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!

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.