Afamelanotide, an agonistic analog of α-melanocyte-stimulating hormone, in dermal phototoxicity of erythropoietic protoporphyria
- PMID: 21073357
- DOI: 10.1517/13543784.2010.535515
Afamelanotide, an agonistic analog of α-melanocyte-stimulating hormone, in dermal phototoxicity of erythropoietic protoporphyria
Abstract
Importance of the field: Afamelanotide, an α-melanocyte stimulating hormone (MSH) agonistic analog is a first-in-class therapeutic. Its application to protoporphyria (PP), a disease associated with absolute sunlight-intolerance is discussed.
Areas covered in this review: The genetics and existing therapy of the inherited disease PP comprising both erythropoietic protoporphyria and X-linked dominant protoporphyria. The physiological and pharmacological actions of α-MSH and afamelanotide including receptor-mediated intracellular signaling and effects of receptor polymorphisms. Adverse effects and safety issues.
What the reader will gain: The clinical severity and the necessity for an effective therapy for the rare disease PP are illustrated by a short, up-to-date portrait. A condensed description of clinically important aspects of α-MSH signaling, physiological, pharmacological and safety issues of afamelanotide applied to humans and the rational for its potential efficacy in PP are given. The different trials of afamelanotide in PP and their most recent results are discussed.
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.
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