Afamelanotide, an agonistic analog of ?-melanocyte-stimulating hormone, in dermal phototoxicity of erythropoietic protoporphyria
2010
Abstract
IMPORTANCE OF THE FIELD]
AREAS COVERED IN THIS REVIEW]
WHAT THE READER WILL GAIN]
TAKE HOME MESSAGE: Although early, results of the first trials of afamelanotide for PP are promising and the risk-safety profile appears favorable today. We expect afamelanotide and analogs thereof to be a prospective therapeutic tool in light-related skin diseases, and in future this drug class might prove effectiveness in other medical conditions.
Mitigating photosensitivity of erythropoietic protoporphyria patients by an agonistic analog of alpha-melanocyte stimulating hormone.
2009
Abstract
Erythropoietic protoporphyria (EPP) is a rare hereditary disorder characterized by dermal accumulation of the photosensitizer protoporphyrin IX. Following sunlight exposure, the resulting photosensitivity is manifested first as pain, later as erythema, edema and dermal lesions. Afamelanotide (Nle(4)-D-Phe(7)-alpha-MSH), a synthetic analog of alpha-melanocyte stimulating hormone and agonist of the melanocortin-1-receptor, promotes melanin synthesis, increasing skin pigmentation. This study examines the efficacy of afamelanotide in preventing symptoms in patients with EPP. A sustained-release subcutaneous implant of 20 mg afamelanotide was administered twice, with a 60-day interval to five EPP patients. Therapeutic efficacy was assessed by a photoprovocation test using standardized white light irradiation, melanin density (MD) determination and daily recording of sunlight exposure and symptoms. From Day 30 to Day 120 tolerance to photoprovocation significantly increased compared with baseline (P = 0.007) and skin MD was significantly higher than that recorded at baseline (P = 0.004). Except for two low-grade pain episodes, patients recorded no phototoxic events past Day 4 of treatment. Tolerance to natural sunlight was up to 24 times longer than prior to therapy. The findings demonstrate beneficial effects of afamelanotide in patients with EPP. Due to the limited number of patients enrolled and the design being an open-label study, confirmation by a large-scale trial is required.
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