- MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.
MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.
Nature medicine (2018-05-08)
Karine Clément, Heike Biebermann, I Sadaf Farooqi, Lex Van der Ploeg, Barbara Wolters, Christine Poitou, Lia Puder, Fred Fiedorek, Keith Gottesdiener, Gunnar Kleinau, Nicolas Heyder, Patrick Scheerer, Ulrike Blume-Peytavi, Irina Jahnke, Shubh Sharma, Jacek Mokrosinski, Susanna Wiegand, Anne Müller, Katja Weiß, Knut Mai, Joachim Spranger, Annette Grüters, Oliver Blankenstein, Heiko Krude, Peter Kühnen
PMID29736023
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.
MATERIALS