Cystine depletion of cystinotic tissues by phosphocysteamine (WR638)

NEPHROPATHIC CYSTINOSIS is an inborn error of metabolism which is characterized by the intralysosomal accumulation of the disulfide amino acid cystine in most body tissues, which leads to the renal Fanconi syndrome and progressive renal failure; end-stage renal disease occurs bY the end of the first decade of life? The cause for the cystine accumulation and renal failure is not known; however, since sulfhydryl reactive agents and disulfides can induce the Fanconi syndrome in experimental animals,'-' reduction of the intracellular cystine content in these patients has been suggested as a potentially beneficial therapy. We 3 and others ~ a have suggested cysteamine (2-aminoethanthiol) as a possible therapeutic agentl following the demonstration that cysteamine produces rapid depletion of Cystine in cystinotic tissues both in vivo and in vitro. Since cysteamine is a free-thiol compound, it has a highly.disagreeable odor and taste which have precluded its use in some patients. We here report satisfactory cystine depletion of cystinotic tissues using the phosphorothioester of cysteamine, WR 638. This agent lacks the Objectionable odor of cysteamine and is less toxic; it appears to be as efficient in producing cystine depletion as the parent compound.