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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Antigens, Neoplasm, Appetite Regulation, Dose-Response Relationship, Drug, Female, Injections, Intraperitoneal, Male, Metabolism, Mice, Mice, Inbred C57BL, Mice, Nude, Neurons, Prader-Willi Syndrome, Pro-Opiomelanocortin, Proteins, Receptor, Melanocortin, Type 4, Structure-Activity Relationship, alpha-MSH.
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Are magel2-null mice hyper-responsive to setmelanotide , a melanocortin 4 receptor agonist? Context: α- and β-melanocyte-stimulating hormones (MSH) are derived from pro-opiomelanocortin (POMC) and are the natural agonist ligands of the melanocortin 4 receptor, a key regulator of energy homeostasis. Recent rodent and human data have implicated the MAGEL2 gene, which may regulate activation of POMC neurons, as a significant contributor to the metabolic symptoms observed in Prader-Willi Syndrome (PWS). Firstly, patients with protein truncating mutations in MAGEL2 exhibit numerous clinical characteristics of PWS. Secondly, Magel2-null mice may not normally activate MC4 receptors, as they are defective in the activation of their POMC neurons and hence may fail to normally release the POMC-derived MC4 receptor agonist ligands α- and β-MSH. Magel2-null mice represent a tractable animal model for the metabolic and appetitive imbalance seen in patients with PWS. We tested a dose titration of the MC4 receptor agonist setmelanotide, in development for rare monogenic forms of obesity, in Magel2-null mice. We show that Magel2-null mice are hypersensitive to the appetite suppressing and metabolic effects of setmelanotide.
assistant
Setmelanotide may be a useful investigational hormone/neuropeptide replacement therapy for PWS and rare monogenic forms of obesity exhibiting impaired function of POMC neurons. Final Decision: yes