A DOUBLE-MASKED CONTROLLED RANDOMIZED CLINICAL TRIAL OF TOPICAL CYSTEAMINE

肾病综合征是一种常染色体隐性遗传性储存症。 非蛋白胱氨酸在细胞溶酶体内积聚的疾病 由于溶酶体的半胱氨酸运输存在缺陷。眼部表现 包括畏光，角膜、结膜和虹膜中的晶体沉积， 视网膜色素脱失。系统性并发症包括 范科尼综合征和肾功能衰竭。 九年前，半胱胺，一种从细胞中耗尽半胱氨酸的游离硫醇， 被引入到膀胱虫病患者的治疗中。尽管患者有 改善生长和稳定肾功能，没有明显的 对角膜晶体堆积的影响。最近的研究表明， 在组织培养的角膜细胞中，胱氨酸很容易被 半胱胺的引入，使眼科外用成为可能 半胱胺来绕过体液路线。经过适当的动物 测试并发症的研究没有发现任何并发症，我们开始了双面具 临床试验，以测试外用半胱胺(0.1%)对人体的疗效。 14名年龄小于3岁的患者被纳入并随机分配到 0.1%的半胱胺。5名患者表现出晶体显著减少。 用半胱胺治疗的眼睛。为了测试提高利率水平的效果 人体内半胱胺滴眼液的浓度，一项毒性研究 在兔子身上进行。该研究未显示不良反应。结果是 允许人类使用的浓度增加到0.5%，所有 接受0.1%半胱胺治疗的患者改用0.5%。一项额外的 5名年轻患者的治疗眼明显减少。因此， 20名年轻患者中，12名成功破解了密码；其余8名患者中， 2人死亡，3人停止用药，2人仍在试验中，1人已 接受治疗的时间太短，无法判断。由于在比赛中取得的成功 年轻患者，这项研究扩大到包括老年患者，3到 31岁。最令人兴奋的发现是：14名患者 在接受治疗的眼睛中晶体显著减少，以及 舒适性的改善，即缓解疼痛和畏光。这项研究有 显著提高了成功人士的生活质量 治疗过的病人。

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. Systemic complications include the Fanconi syndrome and renal failure. Nine 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%) in humans. Fourteen patients of ages less than 3 years were enrolled and randomized to 0.1% cysteamine. Five patients showed a significant decrease in crystals in the cysteamine-treated eyes. In order to test the effects of increasing the concentration of cysteamine eye drops in humans, a toxicity study was performed in rabbits. The study showed no adverse reactions. The results permitted an increase in the concentration to 0.5% for human use, and all patients receiving 0.1% cysteamine were switched to 0.5%. An additional five young patients showed a significant decrease in treated eyes. Thus, of 20 young patients, 12 successfully had the code broken; of the remaining 8, 2 died, 3 discontinued medication, 2 are still in the trial, and 1 has been receiving treatment too short a time to tell. Due to the success in the younger patients, this study was expanded to include older patients, 3 to 31 years old. The findings have been most exciting: Fourteen 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.