MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency
K Clément, H Biebermann, IS Farooqi… - Nature medicine, 2018 - nature.com
Nature medicine, 2018•nature.com
Genetic defects underlying the melanocortin-4 receptor (MC4R) signaling pathway lead to
severe obesity. Three severely obese LEPR-deficient individuals were administered the
MC4R agonist setmelanotide, resulting in substantial and durable reductions in hyperphagia
and body weight over an observation period of 45–61 weeks. Compared to formerly
developed and tested MC4R agonists, setmelanotide has the unique capability of activating
nuclear factor of activated T cell (NFAT) signaling and restoring function of this signaling …
severe obesity. Three severely obese LEPR-deficient individuals were administered the
MC4R agonist setmelanotide, resulting in substantial and durable reductions in hyperphagia
and body weight over an observation period of 45–61 weeks. Compared to formerly
developed and tested MC4R agonists, setmelanotide has the unique capability of activating
nuclear factor of activated T cell (NFAT) signaling and restoring function of this signaling …
Abstract
Genetic defects underlying the melanocortin-4 receptor (MC4R) signaling pathway lead to severe obesity. Three severely obese LEPR-deficient individuals were administered the MC4R agonist setmelanotide, resulting in substantial and durable reductions in hyperphagia and body weight over an observation period of 45–61 weeks. Compared to formerly developed and tested MC4R agonists, setmelanotide has the unique capability of activating nuclear factor of activated T cell (NFAT) signaling and restoring function of this signaling pathway for selected MC4R variants. Our data demonstrate the potency of setmelanotide in treatment of individuals with diverse MC4R-related pathway deficiencies.
nature.com