Stadtspital Triemli, Central Laboratory, Zurich, CH-8063, Switzerland.
Expert Opin Investig Drugs. 2010 Dec;19(12):1591-602. doi: 10.1517/13543784.2010.535515. Epub 2010 Nov 13.
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.
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.
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.
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.
阿法美拉汀，一种α-促黑素细胞激素（MSH）激动剂类似物，是一种首创的治疗方法。本文讨论了其在原卟啉症（PP）中的应用，PP 是一种与绝对阳光不耐受相关的疾病。
包括红细胞生成性原卟啉症和 X 连锁显性原卟啉症在内的遗传性疾病 PP 的遗传学和现有治疗方法。α-MSH 和阿法美拉汀的生理和药理作用，包括受体介导的细胞内信号转导和受体多态性的影响。不良反应和安全问题。
通过简短的最新概述说明了罕见疾病 PP 的临床严重程度和对有效治疗的必要性。对 α-MSH 信号转导的临床重要方面进行了简明描述，对应用于人体的阿法美拉汀的生理、药理和安全性问题及其在 PP 中潜在疗效的合理性进行了说明。讨论了 PP 中阿法美拉汀的不同试验及其最近的结果。
尽管早期，但阿法美拉汀治疗 PP 的首次试验结果令人鼓舞，目前风险-安全状况似乎良好。我们预计阿法美拉汀及其类似物将成为光相关皮肤病的有前途的治疗工具，并且在未来，此类药物可能在其他医疗条件下证明其有效性。
