Cystinosis family conferences
offer researchers wonderful opportunities to gather data and information from
patients and from their families while they are all together for support and
education. It is unusual for that many cystinosis subjects to be in the same
geographic location for that long a time. The researchers have an opportunity
to ask questions, do physical examinations, take blood and gather data, and
then gather more data if there is a need.
Conferences have made
published research papers possible. Published research papers spread interest
in cystinosis, and creates more research. Conferences have also given the
researchers and families an opportunity to know one another. The researchers
have a chance to differentiate the patients and their families from the
research data they have read and collected. The researchers get to see the data
as a living and thriving group of people. They get to see the hopes, fears, and
joys. The families, on the other hand, get to see the researchers as real
people, who don't always wear white lab coats and carry needles, who have
families of their own. To the researchers and to the families who dedicate
their vacation time to research and being researched, thank you for furthering
the cause of finding a cure for cystinosis.
Anne Hotz, MA
Gastric Research Study (08/01/2003)
This study will evaluate the absorption/effect of cysteamine administered into the stomach, jejunum, and colon. This study is being funded entirely by the newly formed Cystinosis Research Foundation, Founded by Nancy and Jeff Stack***Sept 2003 Update***
Dr. Dohil is ready to begin the study and patients interested in participating.
Click Here to Read the Details
U.S. Cysteamine Eye Drop Development (02/27/2003)
This document is courtesy of Sigma-Tau Pharmaceuticals) and basically is a history of the how Sigma Tau Pharmaceuticals got involved with and eventually came to produce the eyedrops for our paitents with cystinosis.
Update from Dr. Dohil on the Prilosec Study (12/20/2001)
The cystinosis study is coming on well. We have recruited our required quota of patients. Because the study is in two parts, each separated by a 4 month time interval, any useful interpretations of our study will be difficult to make at this point. It does seem however that a number of children did have a significant and rapid increase in acid output immediately after cystagon was administered. This is very likely to contribute in some way to the terrible GI symptoms that these children suffer. In addition a number of children have demonstrated symptomatic relief since starting medications to suppress acid production.Ranjan Dohil, M.D.
University of California, San Diego, School of Medicine
Update on Research from Dr. Jess Thoene (10/2001)
We all recognize that the ultimate goal of the Cystinosis Foundation and the investigators studying cystinosis is to perfect a permanent cure that does not require administration of unpleasant tasting medicine or eyedrops. Clearly, gene therapy is the only avenue yet known that offers that possibility, but successes in this field are few, and risk attaches to the clinical trials. The standard approach is to progress from rodent to primate in showing efficacy and safety, before clinical trials in patients can be allowed.Recent studies have shown that rodents are so different from primates that lessons learned in mice may not translate to monkey or man. We are therefore planning a series of trials in rhesus monkeys to determine if we can get expression of a reporter gene in monkey kidney. Kidney tissue has been very difficult to breach, and genes placed there often don't function. We are fortunate in having the Tulane Primate Center as part of this complex, and have applied for venture funding to do a small pilot study there in collaboration with the primate specialists. They include skilled surgeons and veterinarians who will help us with the gene delivery. If we are successful, then more extensive primate studies can be undertaken, and support sought from NIH.
Jess Thoene, M.D., Professor and Chair, Human Genetics Program,
Hayward Gentics Center,
Tulane University Medical Center, School of
Medicine
PRILOSEC
STUDY
Three patients have
now completed the first part of the study of Omeprazole (Prilosec) to
counteract the gastric symptoms that some patients have with Cystagon. Four
more patients are scheduled for September 2001.
We are anxious to identify more
children for this study. Dr. Dohil believes the most difficult part of the
study for children is swallowing a nasogastric tube. He wonders if some parents
have decided against the study for this reason. Dr. Dohil was surprised to find
how many of the children with cystinosis have a G-tube in place. In these
children it is not necessary to use a nasogastric tube. In fact it is easier to
do the study through the G-tube!
Anyone
wanting more information should contact Dr. Dohil at pager (858) 493-3706 or
rdohil@ucsd.edu.
Steriod Free Post Transplant
Therapy
Article on the Business Wire regarding the Theriod
Free Post Transplant Therapy Study conducted by Dr.'s Sarwal and Salvatierra
among others from Lucile Packard Children's Hospital at Stanford University and
the Stanford University School of Medicine.
Read the Article
Annual Report to the Cystinosis Foundation (02/2000)
With the support of the Cystinosis Foundation we have made significant progress in the construction of an animal model for cystinosis. We screened a mouse library for the mouse homologue of the human CTNS gene, and were successful in identifying a full length cDNA transcript which is approximately 80% homologous with the human CTNS cDNA. We have now placed that transcript into a suitable vector with two exons deleted, such that it will not function when expressed in a mouse cell. The vector construct has been given to the core laboratory at the University of Michigan where the construct will be transfected into pleuripotent embryonic stem cells. Clones of each cell so treated will then be screened to determined if homologous recombination has occurred. Those where success has been demonstrated by PCR of the two ends of the transcript will then be placed into pseudo-pregnant mice and the progeny screened for the presence of chimerism. When chimeric mice have been successfully identified they will be crossbred, with the goal of producing mice heterozygous for the knock-out for CTNS. Ultimately breeding two heterozygotes will lead to production of cystinotic mice. Once these mice have been obtained, their organs will be studied for cystine content, and then they will be ready for attempts at correcting the knock out defect via gene therapy.Additionally, we have demonstrated that gentamycin, an aminoglycoside antibiotic, corrects the cystinotic phenotype in cultured cystinotic cells which express a premature stop codon. This correction has been demonstrated in another model systems, but to our knowledge this is the first time that correction by this means has been achieved in the cystinotic mutation. Whether it will lead to any innovative therapy in cystinosis remains an unanswered question, although the nephrotoxicty of aminoglycoside antibotics is well known, suggesting that it will not be suitable in the current form.
RESEARCH UPDATE (11/2000)
With the long term support of the Cystinosis Foundation we have undertaken creation of a knock-out mouse for the lysosomal cystine transport gene. The mouse homologue has been isolated, the knock-out vector constructed, blastocysts injected, and chimera mice created. Now we are in the phase in which we see if germline transmission has occured. When successful, these mice will enable pharmacokinetic studies of cysteamine to optimize dose schedules, and to possibly improve treatment of the eyes. More importantly, they will permit foundational studies in gene replacement with an ultimate aim of producing a permanent correction.
Jess Thoene, M.D., Professor and Chair, Human Genetics Program, Hayward
Gentics Center,
Tulane University Medical Center, School of Medicine
Muscle Weakness or Swallowing
Problems?? (Posted
1/22/98)
Dr. Doris Trauner [University of California, San Diego, Pediatric Neurology] has been studying the neurologic consequences of cystinosis for several years. She and her colleagues are interested in the problems with muscle weakness and swallowing that some adults with cystinosis are experiencing.In particular, they are very interested in learning more about the cause of the late onset muscle weakness and swallowing problems. In order to do this, Dr. Trauner and her colleauges would like to perform neurological examinations, electromyograms, and nerve conduction velocity studies on individuals who are experiencing one or both of these problems. If you are interested, or know someone who might be interested, in participating in the testing to find out more about muscle weakness and swallowing problems, please contact Dr. Trauner's research group at (619) 587-4020.
Investigators at the National Eye Institute and the National Institute of Child Health and Human Development are working with a pharmaceutical company to prepare cysteamine eyedrops for testing in cystinosis patients. This is the first step in an attempt to bring an eyedrop preparation to New Drug Approval by the Food and Drug Administration, which would mean that the eyedrops could be prescribed by any licensed physician. The sponsorship of this venture represents an act of good will, since the small patient population makes this effort financially unprofitable. Current hopes are to begin a study of the new eyedrops in the summer of 1997. Cystinosis patients with severe pain due to corneal crystals may contact the NIH through the Cystinosis Foundation.- William Gahl, M.D., Ph.D.
Head, Section on Human Biochemical Genetics, NICHD