As part of a phase II study at Charité - Universitätsmedizin Berlin and the Berlin Institute of Health, two obese patients with a rare genetic disorder were given a drug treatment to stimulate the satiety center in the brain. After only a few weeks, both patients, which were severely hyperphagic before the study start, showed a normalization of their hunger feeling as well as a significant reduction of body weight. Results from this study have been published in the New England Journal of Medicine.
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Our understanding of the factors involved in the dysregulation of normal body weight remains rudimentary. However it is known that mutations in certain genes play could lead to the development of early onset obesity due to a severe hyperphagia. MC4R is one example; it provides the blueprint for the melanocortin-4 receptor (MC4R), which regulates energy balance and weight. Activation of the receptor by MSH (melanocyte-stimulating hormone) leads to a reduction in the sensation of hunger. Patients deficient in MSH show severe hyperphagia, and develop obesity within the first months of life.
The study team, led by Dr. Peter Kühnen—a physician at the Institute for Experimental Pediatric Endocrinology—treated two patients with congenital proopiomelanocortin (POMC) deficiency. POMC is a precursor of the hormone MSH, and is secreted by the hypothalamus; deficiency causes significantly increased hunger. The researchers set out to test whether the new drug might replace the effect of the prohormone through targeted activation of the satiety center. First effects were recorded within a few weeks of the start of treatment. Patient 1, whose starting weight was 155 kg (342 lbs), achieved a total weight loss of 51 kg (122 lbs) over a period of 42 weeks; patient 2 (starting weight 152.8 kg (337 lbs)) lost a total of 20.5 kg (45 lbs) over the course of 12 weeks.
"Our study results confirm the crucial role of the MC4R signaling pathway in appetite regulation, and represent an important contribution to our understanding of the fundamental processes involved in the control of body weight" says Dr. Peter Kühnen. He goes on to add: "It currently remains unclear, however, whether this treatment will be of benefit to patients whose obesity has no clear genetic cause. Further studies will be needed to elucidate this."
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Kühnen P et al. Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist. New England Journal of Medicine, Published July 21 2016. doi: 10.1056/NEJMoa1512693