Nephropathic cystinosis was long considered primarily a renal disease, but it's now recognized as systemic disorder which eventually effects many organ systems. A certain portion of post-transplant patients develop retinal blindness and corneal ulceration, muscle weakness and wasting, difficulty swallowing, diabetes due to destruction of the pancreas, infertility (in males) and, rarely, central nervous system deterioration. These problems generally occur in the second, third, or fourth decade in patients who never received cysteamine therapy. All of the patients over age 30 seen at the NIH have experienced a major, lifestyle-altering complication of the disease, and the evidence suggests that the complications are progressive in nature.

The only possible countermeasure against this progression is to attack the cystine accumulation with cysteamine, or Cystagon. This drug, approved for use in humans in August 1994, reduces the cystine content of cultured cells by over 90%. When given orally to cystinosis patients, the white blood cell cystine concentration can be lowered to 5-10% of the untreated level, and this suggests that other cells, tissues, and organs are depleted of their cystine as well. In fact, there is substantial evidence that long-term oral cysteamine therapy depletes cystinosis patients' muscle of cystine, and the liver and kidney appear to benefit as well.

Functionally, chronic oral cysteamine therapy has been shown, in three different studies, to retard deterioration of kidney function and to enhance the growth of cystinosis patients. In the most recent study, cysteamine therapy was demonstrated to increase renal function in the first three years of life. Long-term oral cysteamine therapy was also shown to prevent the need for thyroid hormone replacement in many cystinosis patients. Finally, topical cysteamine eyedrops dissolve corneal crystals and relive photophobia.

With all this evidence that cysteamine may help preserve non-renal tissues, we at the NICHD began treating post-transplant patients. We have now treated 21 individuals for more than 5 years with cysteamine. Only 5 of these patients had significant complications of cystinosis, and four of the five had their complications before starting cysteamine. In contrast, 13 of 28 patients treated for less than 5 years experienced a significant complication with cystinosis. In view of the harmful effects of chronic cystine accumulation, and the indications of the effectiveness of cysteamine therapy in various tissues and organ systems, oral cysteamine should be considered for use by post-transplant cystinosis patients. It is already treatment of choice for pre-transplant patients throughout the world.

            - William A. Gahl, M.D., Ph.D.

Cystinosis Central | Cystagon