| Literature DB >> 29736023 |
Karine Clément1, Heike Biebermann2, I Sadaf Farooqi3, Lex Van der Ploeg4, Barbara Wolters2, Christine Poitou1, Lia Puder2, Fred Fiedorek4, Keith Gottesdiener4, Gunnar Kleinau5, Nicolas Heyder5, Patrick Scheerer5,6, Ulrike Blume-Peytavi7, Irina Jahnke7, Shubh Sharma4, Jacek Mokrosinski3, Susanna Wiegand8, Anne Müller2, Katja Weiß9, Knut Mai6,10, Joachim Spranger6,10, Annette Grüters11, Oliver Blankenstein2, Heiko Krude2, Peter Kühnen12.
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.Entities:
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Year: 2018 PMID： 29736023 DOI： 10.1038/s41591-018-0015-9
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440