09 May New Hope For Patients With Rare Form of Overeating Disorder

Posted at 13:10h in Author Interviews, Genetic Research, Weight Research by

MedicalResearch.com Interview with:
“Mmm...hamburgers” by jeffreyw is licensed under CC BY 2.0Dr. Peter Kühnen
Institute for Experimental Pediatric Endocrinology
Charité Universitätsmedizin Berlin
Berlin Germany 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: We are focusing our interest on rare monogenic forms of obesity.

The hormones leptin and MSH are playing a pivotal role for the regulation of satiety and body weight. Mutations within this pathway, e.g. in the leptin receptor gene, are leading to severe hyperphagia and early onset obesity.  Although tremendous effort it is extremely difficult for the affected patients to stabilize their body weight for a longer period of time. For this reason it has been analyzed within this investigated initiated trial whether patients with a leptin receptor mutation benefit from a treatment with the MC4R agonist setmelanotide. The treatment led to a reduction of the initially increased hunger feeling and to a reduction of body weight. Additionally, we identified molecular evidences that a specific signaling cascade of the MSH receptor (MC4R) is of importance for the regulation of body weight.

MedicalResearch.com: What should readers take away from your report?

Response: Monogenic forms of obesity are rare. Severe hyperphagia due to missing satiety signals within in a specific pathway are leading to severe hyperphagia and early onset obesity. Now there is evidence that at least patients with a lack of the satiety signal MSH (POMC gene mutation) and patients with an impaired function of the leptin receptor might benefit from a pharmacological treatment option with the MC4R agonist. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: Additional studies are needed to gain further information about the efficacy/ safety of this MC4R agonist in patients with an impaired function of the so-called leptin-melanocortin signaling cascade. Furthermore it will be analyzed to which extend the different signaling capacities of the MC4 receptor are of importance for the regulation of body weight. 

Citations: 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. MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. Nature Medicine, 2018; DOI: 10.1038/s41591-018-0015-9 

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Last Updated on May 9, 2018 by Marie Benz MD FAAD

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