CYSTEINE THERAPY FOR ERYTHROPOIETIC PROTOPORPHYRIA

红细胞生成性原红细胞增多症(EPP)是一种血红素的孤儿疾病 代谢，其中的铁络合酶是缺陷的。这种酶 缺陷会导致原卟啉的积累，这是一种 光敏剂，导致瘙痒、灼热和肿胀的症状 这种遗传病的特征是暴露在阳光下的皮肤。在许多 患者这种光敏性是如此严重，以至于他们必须严重地减少 他们要到户外去。到目前为止，这种基因缺陷还没有治疗方法。 防晒霜在防止晒伤方面非常有效，但在EPP中没有提供保护。 由于EPP中的光敏反应是由激发态激发的 物种(自由基、单线态氧等)由原卟啉在 光和氧的存在，这些化合物能有效地防止 光敏性必须具有抑制这些物种的能力。其中一些 含硫的辐射防护剂已被证明是非常有效的。 兴奋的物种灭绝剂，在动物模型中，已经阻止了 卟啉的光敏化作用：然而，所研究的不是 被批准供人类使用。因此，我们建议测试氨基酸半胱氨酸， 它在动物模型中被发现是一种有效的辐射防护剂， 并且是无毒的，正在进行临床试验，看看它是否可以防止 EPP中的光敏性。我们在4个月中通过问卷调查获得了证据 患者这种治疗的疗效：在这项拟议的试验中，要更多 牢固树立效能，将采用客观的评价方法-- 用感光法测定红斑形成的时间 半胱氨酸治疗前和治疗期间。鉴于这一目标的成功 评估后，我们将研究半胱氨酸对30名患者的影响 一种安慰剂对照的交叉设计。

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.