A DOUBLE-MASKED CONTROLLED RANDOMIZED CLINICAL TRIAL OF TOPICAL CYSTEAMINE

肾病型胱氨酸病是一种常染色体隐性遗传贮藏

Nephropathic cystinosis is an autosomal, recessively inherited storage disease in which nonprotein cystine accumulates within cellular lysosomes due to a defect in lysosomal cystine transport. Ocular manifestations include photophobia; crystal deposits in the cornea, conjunctiva, and iris; and depigmentation of the retina. Ten years ago cysteamine, a free thiol that depletes cystine from cells, was introduced in the therapy of cystinotic patients. Although patients had improved growth and stabilized renal function, there was no noticeable effect on the accumulation of corneal crystals. Recent studies showed that corneal cells in tissue culture are readily depleted of cystine by the introduction of cysteamine, making feasible the use of topical ophthalmic cysteamine to circumvent the humoral route. After appropriate animal studies to test for complications revealed none, we began a double-masked clinical trial to test the efficacy of topical cysteamine (0.1% and 0.5%) in humans. To date, in 14 of 29 young patients the code was successfully broken; of the 15 remaining, 2 died, l discontinued medication, and 12 are still in the trial with poor compliance and have not been seen for followup. Because of the success in the younger patients, this study was expanded to include older patients, 3 to 31 years of age. The findings have been most exciting: Twenty-three patients have shown a significant decrease in crystals in treated eyes as well as improvements in comfort, ie, relief of pain and photophobia. This study has resulted in significantly improved quality of life for the successfully treated patients. Because of the success of this clinical trial, and evidence from the cysteamine- benzalkonium trial (Protocol Number 93 EI-0230), the Food and Drug Administration has requested that all patients in this protocol be switched to cysteamine plus benzalkonium and receive medication in both eyes. Each patient then will be judged by a comparison with his or her own natural history.