Mission Accomplished

The first ever Cystinosis Research Foundation International Research Symposium was held in Irvine, California the first week of April. The purpose of the event was to bring together (in one room) all of the researchers, doctors, scientists and geneticists (funded by the CRF---and your direct contributions)in order to update and share information and progress on their studies from the past year. It was a landmark event as most all of these people had never met each other and were not intimately aware of what each other are doing. The event was a huge success. Doctors were asking thought provoking questions, exchanging cards and ideas and a few jabs every now and then---all in the name of progress. There was a positive air in the room and when all the smoke cleared I think we all agree as to the value of the time spent at UC Irvine over those two days. I'd like to start by thanking Danny and Molly Kelly. I dropped a hint that since Chrissy could not attend that the Stacks indicated I could bring a guest. I had barely gotten the words out when he simply said--"I'm in". I really needed someone there with me--the emotional support and thought leadership you gave were remarkable. Thanks DK.

If you really think about the process and how it works, it makes sense. The CRF empowers an independent scientific review board to study the research proposals and decide what get funded--and not everyone who proposes gets funded. The awards are based on the merits of the idea, its relevance, significance, et al. From a strategic perspective I can now see how they are thinking but I don't think that the individual researchers clearly understood what each of the other teams are doing. It makes sense to me now and after attending the event and I can see the importance and significance of the occassion. Mission accomplished! After two very long days of updates and dialogue---we left the event with an even greater feeling of hope for where we are going and the positive direction the CRF is taking towards meaningful progress.

All told we heard 26 different presentations all focused on cystinosis and let me tell you---these people are smart and speak an entirely different langauge than us. After each one, Danny Kelly and I would have to discuss what it was that we thought we had just heard just to write exec summary type of notes. Then we would corner the people who had presented to review what we thought we heard to confirm that we were at least in the ballpark. Many times we were and sometimes we weren't even close. But we got clarity on the ones we couldn't understand---I made sure of that. Danny probably thought I was crazy. What was really neat about it was that once it was over---if you pieced all of the summaries together they told a very logical story. The story starts a little rough but by the end, I was extremely enthusiastic with where this is giong.

Natalie Stack (Natalie's Wish) opened the event with a brief speech and we met the Partington family and their beautiful children Jenna and Patrick---both with Cystinosis. I see a future with The Partingtons, we seem to have a lot in common and similar ideas as to how to move forward. I probably was a little more reserved than normal---but to be honest I was such an emotional wreck during the event that I found myself clammed up. Here are the highlights from the presentations.

(Before you read this on day 1, know that day 2 was THE day that really woke the hope inside of me).

To summarize day 1, I think Danny and I would agree that the theme for the day seemed to be mostly centered on taking the "what we already know" to a higher level. How do we get better blood testing, how do we do better analysis, what have we learned from the data that is now more mature as it relates to CTNS (short for Cystinosis) patients capabilities, future risks, how do we give a better quality of life etc. All of this is fantastic work and very well intended. Quite honestly though---it was a little deflating. A lot deflating. I guess I dont really know what I expected to hear---yes I do---I guess it was more what I WANTED to hear and on the first day I didnt hear it. Not only did I not hear it but I was presented with data and findings which confirmed a lot of what we thought we already knew and how cruel and difficult Holts life will be. It's just so hard to swallow---Holt makes us so happy, he's so special to us---he has such a warm spirit and a "seize the day happiness" that its just hard to come to grips with how sick he is. It's really hard---I'm just not there yet, not even close.

Day1-
-Dr. Trauner presented her findings on Mitochondrial Dysfunction in Cystinosis Myopathy. Essentially, it described many of the muscular wasting symptoms Holt will have as an adult and the correlation of those issues with medicinal compliance. Muscle wasting, problems swallowing, lack of hand strength, weakness in hip abduction etc. Interestingly, her studies did show that medicine compliance postively correltes with either improved strength or a much slower deterioration of the muscles. HGH (human growth hormone) will be an option but there will be a tradeoff---HGH will help Holt grow and will help his muscles develop but it will also speed up the need for a kidney transplant. Danny and I were able to have a hallway conversation with a leading pediatric nephrologist on topic---a very worthwhile discussion and at the end of the day it's going to be a very difficult decision for Chrissy and I to make.

-Dr. Gasnier is working to identify a different lysosomal transport mechanism for Cystinosis. To simplify what was an extremly difficult presentation to follow---your organs are made up of cells, inside those cells are lysosomes which contain cystine. Cystine needs to exit the cells but cannot in Cystinosis patients. It causes the cells to die which form the crystals which destroy his organs. This team is studying alternative exit paths which would allow this exit to happen for those with Cystinosis.

-Dr. Chiaverini presented on molecular mechanisms of Hypopigmentation in Cystinosis. Essentially, she is trying to understand why most Cystinosis patients are so light skinned and its relation/impact on other areas of the body---namely skin cancer. If she can draw the appropriate conclusions it could lead to treatments which would decrease his risk.

-Dr. Phillips is working to build a yeast model for Cystinosis. Yeast models have consistently proven to lead to optimized research methods and tools and this team out of Rochester, NY successfully built such a model for Battens disease. It just so happens that they have shown that the amino acid sequence for Battens is 31% identical and 47% similar to that of Cystinosin. If successful---it could lead to more effective medicines for Cystinosis patients.

-Dr. Kleta gave insights into adult lysosomal staorage disorder. Effectively, he gave the data which confirms what just isn't really easy to listen to when you know that its waiting for your child. It's all bad. Really bad. I'd rather not write about it.

-Dr. Ballantyne gave her findings on cognitive domain of Executive functioning in Cystinosis. This was a HUGE help as is gives us insight into the skills which are naturally lacking in those CTNS positive. It might not sound at first like a big deal but there are many subtleties which could be easily confused by teachers and attributed to willful behavior rather than cognitive impairment. This is groundbreaking as it will help us better understand the best type of education for Holt and how to work with him to help him be the best he can be. He will not only have the gross and fine motor skills issues which we knew about but also deficits in visualspatial and visual memory. He will lose his temper over seemingly little things and will lack impulse control---often acting before thinking. He will have trouble resuming after a disctraction, sustaining attention, organizing, planning and will make careless mistakes. He will know what to do, but wont do it and will lack function in initiation, goal setting, independent thought etc. Not easy to hear but incredibly helpful to us--as parents. Incredibly helpful.

-Dr. Fidler is researching different methods to store his blood for testing. Might not sound like much-- but to us its huge. I wont go into specifics, but suffice it to say that when we get his blood analyzed each quarter to review his baselines---its an extremely difficult process--one which requires excessive attention to detail--the type of detail that most labs dont use any more due to advances in testing machinery---which for CTNS patients are of little use. As a result, if a mistake is made---which it has been each quarter so far---he has to go back down to have blood drawn again which is painful and traumatic for him. In tandem to her research, the Dr's at UCSD are studying the mass spectrometric analysis of Cystine dynamics. I'm not able to speak too intelligently on Mass spectometry but I do know that if they are successful that they could completely uravel many of the confounding mysteries that the disease presents to reseachers today.

-The last presentation of the first day was that of Dr. Dohil. He gave his findings on the human trials of the 12 hour dose of Cystagon (the drug he currently gets every six hours). The patent for this drug was recently sold to Raptor Pharmaceutacles and could be ready in the next 3-4 years. Simply put, this would completely change his life....in a good way.

Day 2- THE day.
I have to be careful with some of what I write here---these presentations were based on progressive testing techniques---gene therapy, cell fusion, stem cell research, nano-technology. You hear a lot of these buzzwords and about the future of research---the conclusions seemed to be extremely positive. Extremely positive.


Sit down for this one----
-Stephanie Cherqui and the team at The Scripps Institute successfully cured a mouse with Cystinosis. Multiple mice with Cystinosis. This is a remarkable accomplishment for a few reasons. First- building a successful mouse model just doesn't happen very often. The process most often fails in research labs because to make it happen, you first have to find a virus which can successfully carry the disease and "drop it off" into the mouse---essentially, give the mouse the disease. They did that.

Once, the mouse has the disease you then can go to work. But what often complicates cure research are the number of variables and affected strands of DNA researchers are working with---the number of variables is often so high that what may work in one mouse doesn't work in others. With Cystinosis, it SEEMS that the number of variables is actually quite low----that's a big assumption so we can't get too excited yet. BUT what she did next is what really gave me chills. She was successfully able to give the mice a bone marrow stem cell transplant (BMSCT) which, when done, reduced the cystine levels to at or below levels of normal. Of course, I pretty much lost it at that point so I immediately cornered the Director after her presentation. I informed him that I was a parent and that I needed to better understand what I had just heard---if I heard correctly, you gave a BMSCT to a mouse and when you did the cystine essentially disappreared---you cured the mouse---is that what I heard?" He looked me straight in the eye and said---"now listen, I have to be extremely careful with what I say to you right now. As a scientist, I have to be ultra-conservative when speaking--espescially to a parent or donor as it would be cruel to give false hope and I would lose all credibility if I were somehow perceived to be influenced by a donor. Let me say this----I am extremely enthusiastic about what we have done---in fact---I think we can have this at clinical trial in the next 5-7 years".

Now what that means is that they still have to go back and perfect their mouse model and then it has to be tested on primates----IF successful it would then go to human trial. BIG IF. BIG IF. To think he could be cured---I just can't go there. It brings me to tears every time I think about it.

-Dr. Jester presented his findings on confocal microscopy. If you recall, without hourly eye drops to dissovle crystals in his eyes, Holt will go blind. Dr. Jester believes he can work with nano-technology which could allow Holt to only have to take the eye drops once a month. Think of it as slow release eye drops.

-Claire Hippert presented their findings on gene transfer studies the initial results seem to indicate that they have a proof of concept that gene transfer could correct (not cure, but correct) the defective lysosomal transport mechanism. If this could be developed fast enough it would essentially halt the progression of the disease. But her findings showed that it was age dependent so it would have to be done while he is young...but he's only 2.5

-Dr. Willenburg who quite honetly does not believe that the BMSCT process performed by scripps will work (he said he proved as such in his Doctorial thesis that bone marrow is not an effective conduit for stem cell transplantion) is working on stem cell research to cure the Fanconi syndrome affliction of the disease. Fanconi syndrome is what ultimately leads to kidney failure.

-Dr Wilmer successfully created stem cells which did not die. This one was so far over my head that I couldn't effectively write the summary---but it got resounding reaaction from the crowd and seemed to indicate that they could unravel the kidney dysfunction in CTNS patients.

There were another 4-5 studies focused on gene therapy, cell fusion and organ reproduction that were really interesting but incredibly complex to understand and even more difficult to write about. Quite frankly, I was so excited at this point and also so brain fatigued that it became harder and harder to concentrate. I just want to say this. The funds being raised by the CRF and the organization and focus they provide are like nothing I have ever seen. To have come so far in such a short amount of time is indescribable but apparent when you meet the Stacks and this team of people that they have organized to attack this insiduous disease. Will we ever find a cure? I don't know and don't want to get my hopes up too high. I do know though that Holt's life will get better than what it is today and that someday in the future other children with CTNS will have a much better life as a result of these efforts. Thank you so much for all of your support, we are so incredibly grateful that you take the time to read, to respond, to call, to write and to encourage us. Your actions matter to us, they make a difference--a real difference. We are truly and deeply appreciative and we have a renewed Hope for Holt.

Good night-
Jason