CYSTEINE THERAPY FOR ERYTHROPOIETIC PROTOPORPHYRIA

红细胞生成性原卟啉症（EPP）是一种血红素孤儿病 代谢，其中酶亚铁螯合酶是有缺陷的。 这种酶 缺陷导致原卟啉的积累， 光敏剂，导致瘙痒、灼热和肿胀症状 这种遗传病的特征性皮肤暴露在阳光下。 在许多 患者的这种光敏性是如此严重，他们必须严格限制 他们去户外。 目前还没有治疗这种遗传缺陷的方法。 防晒霜在防止晒伤方面非常有效，但在EPP中没有保护作用。 由于EPP中的光敏反应是由激发的 物种（自由基、单线态氧等）由原卟啉产生， 光和氧气的存在，化合物有效地防止 光敏性必须具有淬灭这些物质的能力。 一些 含硫的辐射防护剂已经显示出非常有效 兴奋的物种淬灭剂，并在动物模型中， 卟啉光敏化：然而，研究的那些不是 批准用于人类。 因此，我们建议测试氨基酸半胱氨酸， 已经发现其在动物模型中是有效的辐射保护剂， 并且无毒，在一项临床试验中， EPP中的光敏性。 通过问卷调查，我们在4个 这种治疗的疗效患者：在这项拟议的试验中， 确立疗效，采用客观评价方法- 通过光试验确定出现红斑所需的时间 在半胱氨酸治疗之前和期间。 鉴于这一目标的成功 评估，然后我们将研究半胱氨酸在30例患者中的作用， 安慰剂对照交叉设计。

Erythropoietic protoporphyria (EPP) is an orphan disease of heme metabolism, in which the enzyme ferrochelatase is defective. This enzyme defect results in the accumulation of protoporphyrin, which acts as a photosensitizer, leading to the symptoms of itching, burning and swelling of light-exposed skin characteristic of this genetic disease. In many patients this photosensitivity is so severe that they must severely curtail their going outdoors. There is as yet no treatment for the genetic defect. Sunscreens, so effective in preventing sunburn, offer no protection in EPP. Since the photosensitivity reactions in EPP are triggered by the excited species (free radicals, singlet oxygen, etc.) produced by protoporphyrin in the presence of light and oxygen, compounds effective in preventing photosensitivity must have the ability to quench such species. Some of the sulfur-containing radioprotectors have been shown to be very effective excited species quenchers, and in animal models, have prevented photosensitization by porphyrins: however, the ones studied are not approved for human use. Thus, we propose to test the amino acid cysteine, which has been found to be an effective radioprotector in animal models, and is non-toxic, in a clinical trial to see if it can prevent the photosensitivity in EPP. We have obtained evidence by questionnaire in 4 patients of efficacy of this treatment: in this proposed trial, to more firmly establish efficacy, an objective method of evaluation will be used - the determination by phototest of the time it takes to develop erythema before and during cysteine therapy. Given the success of this objective assessment, we will then study the effects of cysteine in 30 patients using a placebo-control cross-over design.