Most recent update: Friday, July 20, 2018 - 11:48

Bariatric News - Cookies & privacy policy

You are here

Obesity drugs

MC4R agonist setmelanotide helps patients with genetic obesity

Three severely obese LEPR-deficient individuals were administered the MC4R agonist setmelanotide, resulting in substantial and durable reductions in hyperphagia and body weight

Researchers the Institute for Experimental Pediatric Endocrinology of the Charité - Universitätsmedizin Berlin, Germany, have successfully treated patients whose obesity is caused by a genetic defect. Aside from its beneficial effects on the patients, the researchers also provided insights into the fundamental signalling pathways regulating satiety of the new drug. The results of this research, ‘MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency’, were published in Nature Medicine.

A mutation in the gene encoding the leptin receptor (LEPR) can cause extreme hunger starting with the first months of life. As a result, affected individuals develop extreme obesity during childhood. Increased exercise and reduced caloric intake are usually insufficient to stabilise body-weight. Two years ago, Dr Peter Kühnen and the working group successfully demonstrated that treatment with a peptide, which activates the melanocortin 4 receptor (MC4R) could play a central role in the body's energy metabolism and body weight regulation.

Leptin, which is also known as the satiety hormone, normally binds to the LEPR, triggering a series of steps that leads to the production of melanocyte-stimulating hormone (MSH). The act of MSH by binding to its receptor, the melanocortin 4 receptor (MC4R) which transduce the satiety signal to the body.

However, if the LEPR is defective, the signalling cascade is interrupted. The patient's hunger remains unabated, placing them at greater risk of becoming obese. As part of this current study, researchers used a peptide that binds to the MC4R in the brain, and this activation trigger the normal satiety signal. Working in cooperation with the Clinical Research Unit at the Berlin Institute of Health (BIH), the researchers were able to record significant weight loss in patients with genetic defects affecting the LEPR.

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. The researchers said that compared to formerly developed and tested MC4R agonists, setmelanotide has the unique capability of activating nuclear factor of activated T cell (NFAT) signalling and restoring function of this signalling pathway for selected MC4R variants.

"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," said Dr Peter Kühnen. "We were able to demonstrate that this treatment leads to the activation of a specific and important signalling pathway, whose significance had previously been underestimated."

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 signalling pathway might be suitable candidates for this treatment."

Want more stories like this? Subscribe to Bariatric News!

Bariatric News
Keep up to date! Get the latest news in your inbox. NOTE: Bariatric News WILL NOT pass on your details to 3rd parties. However, you may receive ‘marketing emails’ sent by us on behalf of 3rd parties.