Cystamine and Cystinosis

The purpose of our studies is to discover better drugs for the treatment of cystinosis.  In particular we are focusing on the delivery of cysteamine (cystagon) by cystamine (cystamine will be italicized to distinguish is from cysteamine).   These studies were prompted by the observation that experimental animal can tolerate greater amounts of cystamine versus cysteamine.  Since cystamine acts to deliver cysteamine to the body we postulated that cystamine may be a more effective treatment for cystinosis.  We speculate that cystamine would only have to be given once a day and at a lower dose than cysteamine.  Cystamine also has the advantage of not having the unpleasant odor of cysteamine.

Our studies are currently focused on three aspects of the actions of cystamine and its metabolism.  The first of these is to understand why animal can tolerate greater amounts of cystamine than cysteamine.  We have discovered that cystamine binds to a blood component and then released at a slow rate.   The end result is that cystamine acts as a slow release delivery system.  We have communicated our findings to Dr. Schneider who is performing exploratory studies to investigate the aforementioned mechanism in cystinotic patients.  We believe that it is essential, where possible, to communicate with physician-scientist who can bridge the cap between the lab and the clinic.  Our second discovery has been to show that cystamine prevents acts to prevent the death of cells.  There are many pathways that cells can die by.  It is commonly thought - for historical reasons - that most cells die  in a manner analogous to cells of the immune system.  More recent studies have shown that this is not true.  We have shown that cystamine prevents the form of cells death that is more likely to be acting in the kidneys of patients with cystinosis (see figure).  This is a very important finding.  Understanding the protective mechanism of cystamine has given us better ideas of its unique effects of the body and has suggested some alternate treatment strategies for cystinosis.  The third discovery is the most exciting of all.  We have discovered that cystamine generates a gas that can convert the damaging cystine into cysteine.  Gases have the advantage of diffusing through tissue and thereby acting over a larger area.  This is the reason that gaseous anesthesias are so effective for surgery.   The gas in question can be delivered by a number of other agents that might better treatments for cystinosis.

At present our studies are restricted to test tube studies and cell culture experiments.  The test tube studies ensure that we have the chemistry right.  Chemistry is the basis of all drug design.   The cell culture experiments ensure that we have biology right.  The next phase is to test the above ideas in animals and this is what we are preparing to do.

The above discoveries would not have been made without the vision and support of the Cystinosis Research Foundation.  We are very grateful for the support of the Cystinosis Research Foundation and the cystinosis community.  The above studies will be the basis of an application to the National Institutes of Health latter this year to further fund cystinosis research.

Thomas Jeitner, Ph.D.
Research Assistant Professor
Department of Biochemistry
Medical College of Wisconsin
Milwaukee, Wisconsin

Dr. Jeitner was awarded a two-year grant to study cysteamine and its analogs to determine whether there are better methods of treatment and drug delivery for Cystinosis patients.  Cysteamine is currently being studied as a treatment for Parkinson’s disease and Huntington’s disease.