Researchers from the Institute for Experimental Pediatric Endocrinology of the Charité -- Universitätsmedizin Berlin have fortunately treated patients with genetic obesity using a recent developed drug.
Genetic obesity is obesity caused by a mutation in one or multiple genes that have a relation fat storage and hunger. Aside from its beneficial effects on the patients, the researchers also provided insights into the fundamental signaling pathways regulating satiety of the new drug. The results of this research were published in Nature Medicine.
In this study, a mutation in the gene encoding the leptin receptor (LEPR) leads to extreme hunger starting with the first months of life. As a result, individuals affected developed extreme obesity during childhood. However, for these cases, increased exercise and reduced caloric intake are still not relevant as well as obesity surgery. This explains why a drug-based approach remains a priority.
Furthermore, roughly two years before the study, Dr. Peter Kühnen and team demonstrated that treatment with a peptide, which works to activate the melanocortin 4 receptor (MC4R) that may have a role in energy metabolism in the body as well as body weight regulation.
Leptin, which is known as the satiety (or starvation) hormone, will normally bind to the leptin receptor (LEPR) which then leads to the production of melanocyte-stimulating hormone (MSH). However, if there exists a mutation in LEPR that leads to a functional defect then the signaling cascade is disrupted. This allows the patient's hunger to continue to be unabated, placing the individual at a high risk.
Part of this current study, investigators used a peptide that binds to the MC4R in the brain, and through this activation, it will trigger the normal satiety signal. "We also wanted to determine why the used peptide was so effective and why, in contrast to other preparations with a similar mode of action, it did not produce any severe side effects," explains Dr. Kühnen. "We were able to demonstrate that this treatment leads to the activation of a specific and important signaling pathway, whose significance had previously been underestimated." Dr. Kühnen's team is planning to conduct further research to determine whether other patients might benefit from this drug: "It is possible that other groups of patients with dysfunctions affecting the same signaling pathway might be suitable candidates for this treatment."
Sources: Charité - Universitätsmedizin Berlin