International Research Symposium
CRF International Cystinosis Research Symposium – 2016
By Stephen Jenkins, MD, CRF Board Member
I recently had the privilege of attending the Fifth International Cystinosis Research Symposium. It’s a research meeting held every other year where all the scientists who have received funding from the Cystinosis Research Foundation come together to share their findings. It’s an opportunity for brilliant minds to collaborate toward our ultimate goals of finding better treatments and a cure for cystinosis.
There were a few things that struck me as I listened to the many research presentations. The first is that cystinosis is a COMPLICATED disease. The classical teaching of cystinosis is that loss of the transporter protein “cystinosin” leads to accumulation of cystine in lysosomes, which subsequently leads to cell death and tissue damage. This mechanism is the basis for treatment with cysteamine, which depletes cystine from the lysosome. If this was the only mechanism by which cystinosis caused disease, then cysteamine should have essentially been a cure. But study after study has shown that even with cysteamine therapy, patients progress to develop Fanconi syndrome, renal failure, thyroid disease and muscle wasting, with its host of complications. The CRF has funded numerous basic science studies that have taken a closer look at the biological pathways that are disrupted by the loss of the cystinosin protein. It turns out the cystinosin protein does a lot more than move cystine out of the lysosome.
One common theme at the symposium was the role of cystinosin in a cellular process called “autophagy.” Autophagy literally means “to eat oneself,” and it is an essential process through which cells recycle damaged proteins and organelles to generate nutrients during periods of starvation or stress. Several scientists showed how this process is impaired in cystinosis. Another important cellular process affected by the loss of cystinosin is the mTORC1 pathway, which is involved in sensing nutrient availability and regulating cell growth. Researchers showed that impairment of this pathway has many negative downstream effects in cystinosis and may explain the development of Fanconi syndrome. Yet another important pattern highlighted by researchers was the presence of increased inflammation in cystinosis cells, which may be implicated in muscle wasting and kidney disease.
The next thing that struck me was how important this basic science research is to finding new therapies. Sometimes it is hard for me to see how studying cystinosis in fruit flies or yeast will lead to a new drug. But by studying these complex cellular pathways, scientists have discovered multiple novel drug targets. For example, Dr. Sergio Catz and Dr. Francesco Emma are looking at experimental drugs that could improve the autophagy pathway in cystinosis cells. Dr. Robert Mak has identified multiple inflammatory cytokines that are elevated in cystinosis, and he is studying the effects of FDA-approved drugs that target these cytokines on muscle wasting and renal function. Other researchers are looking at the effects of certain drugs on the mTORC1 pathway. None of these possible therapies would’ve been discovered without first taking a closer look at the cellular level.
Finally, what struck me the most is that there are some very exciting things on the horizon. Dr. Stephanie Cherqui presented an update on stem cell transplantation. Her lab is working tirelessly to improve the process by which the correct cystinosin gene is inserted into a patient’s stem cells. She is on track to submit the application for a human trial with the FDA, hopefully in the fall of 2016. Dr. Ghanashyam Acharya mystified the audience with his nanowafer research, which promises to be an extremely effective tool in treating corneal cystinosis. He predicted starting the human trial by the end of the year. Dr. Francesco Emma has screened 1200 drugs and found 7 new potential candidates for treating cystinosis. One of these drugs may have a better side effect profile than cysteamine, while another drug may act on impaired cell pathways that are not treated by cysteamine. His lab is moving forward in testing these drugs in knockout mice.”
The symposium was an amazing example of research in action. A diagnosis of cystinosis is devastating, but we are fortunate to have such a vibrant community of researchers who are dedicated to finding a cure and better therapies. I want to thank all the scientists, physicians and researchers for their diligent efforts. I also want to thank the many donors whose money has created a steady pipeline of funding so that we can always move forward with research. I especially want to thank Nancy and Jeff Stack without whom none of this would have been possible. Every rare disease needs a CRF and a Nancy Stack.
CRF International Cystinosis Research Symposium – 2014
The Fourth International Cystinosis Research Symposium was held Thursday, March 6 and Friday, March 7, 2014 at the Arnold and Mabel Beckman Center of the National Academies of Science and Engineering Irvine, California. The co-chairs of the conference were Corinne Antignac, MD, PhD, Stéphanie Cherqui, PhD, Julie Ingelfinger, MD and Elena Levtchenko, MD. The mission of the conference is to unite CRF funded researchers in an effort to encourage collaboration and accelerate the research process. This year’s keynote speaker was Dr. Ana Maria Cuervo, MD, PhD a world renowned expert in the field of autophagy.
CRF International Cystinosis Research Symposium – 2012
The Cystinosis Research Foundation recently held its Third CRF International Cystinosis Research Symposium on Thursday, March 29 and Friday, March 30, 2012 at the Beckman Center of the National Academies of Engineering and Science, Irvine, California. We are grateful to our generous sponsors, Raptor Pharmaceuticals Corp. and Sigma-Tau Pharmaceuticals, Inc., and also wish to acknowledge the dedication and commitment of the symposium co-chairs to bring together the most prominent cystinosis researchers to exchange their ideas about promising new study directions. Thank you to Corinne Antignac, MD, PhD, Stephanie Cherqui, PhD, Julie Ingelfinger, MD, Elena Levtchenko, MD, and honorary chairman, Jerry Schneider, MD, for helping to make the symposium a tremendous success. The next symposium will be held in 2014.
CRF International Cystinosis Research Symposium – 2010
The Cystinosis Research Foundation (CRF) sponsored its Second International Cystinosis Research Symposium for researchers and scientists on Thursday April 8 and Friday April 9, 2010 at the Beckman Center of the National Academies of Sciences and Engineering near the University of California, Irvine campus. Over sixty researchers from around the world attended.
Investigators from the United States, Canada, France, Belgium, The Netherlands, Italy, Ireland and Germany presented their current research on cystinosis. All of the research that was presented has received funding support from CRF.
The purpose of the Symposium is to learn about research progress and foster collaborations among the researchers in order to hasten the progress in understanding and treating cystinosis.
Our first Cystinosis Research Foundation International Cystinosis Research Symposium was held in April 2008 at the prestigious Arnold and Mabel Beckman Center of the National Academies of Engineering and Science on the UCI campus. The event was attended by more than 60 researchers from the United States and Europe who have been working to achieve better treatments and a cure for cystinosis. Researchers funded by CRF presented their current bench and clinical studies on cystinosis.
“The symposium was very important for cystinosis because many of the participants began sharing information on their research efforts – information that generally isn’t shared until it’s published, which often takes months or years. This can only help accelerate new medical and scientific advancements we’ve been working to achieve for so many years,” said Dr. Jerry Schneider, co-chairman of the symposium.