CYSTEINE THERAPY FOR ERYTHROPOIETIC PROTOPORPHYRIA

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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.