MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.

Clément, Karine; Biebermann, Heike; Farooqi, I Sadaf; Van der Ploeg, Lex; Wolters, Barbara; Poitou, Christine; Puder, Lia; Fiedorek, Fred et al. · Nat Med · 2018

case_series · Level IV

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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.

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