Study summary · research use only
Targeting the central melanocortin system for the treatment of metabolic disorders
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review, species not specified, discusses preclinical and clinical evidence on the central melanocortin system as a target for metabolic disorders including obesity, cachexia, and anorexia nervosa. It notes setmelanotide's FDA approval in 2020 for certain forms of syndromic obesity, and the 2019 FDA approvals of bremelanotide for hypoactive sexual desire disorder and afamelanotide for erythropoietic protoporphyria-associated phototoxicity, described as demonstrating this peptide class's safety history. The authors review the anatomy and function of the melanocortin system, progress and challenges in developing melanocortin receptor-based therapeutics, and potential metabolic and behavioral disorders that could be addressed by drugs targeting these receptors.
Abstract
A large body of preclinical and clinical data shows that the central melanocortin system is a promising therapeutic target for treating various metabolic disorders such as obesity and cachexia, as well as anorexia nervosa. Setmelanotide, which functions by engaging the central melanocortin circuitry, was approved by the FDA in 2020 for use in certain forms of syndromic obesity. Furthermore, the FDA approvals in 2019 of two peptide drugs targeting melanocortin receptors for the treatment of generalized hypoactive sexual desire disorder (bremelanotide) and erythropoietic protoporphyria-associated phototoxicity (afamelanotide) demonstrate the safety of this class of peptides. These approvals have also renewed excitement in the development of therapeutics targeting the melanocortin system. Here, we review the anatomy and function of the melanocortin system, discuss progress and challenges in developing melanocortin receptor-based therapeutics, and outline potential metabolic and behavioural disorders that could be addressed using pharmacological agents targeting these receptors.
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