Rare Obesity Disorder May Be Treated With New Drug, Study Finds

An experimental drug has shown the ability to cause weight loss in people suffering from obesity due to a rare genetic disorder, caused by a mutation for melanocyte-stimulating hormone (MSH) deficiency, by curbing hunger.

The disorder is caused by mutations in the gene that makes the protein proopiomelanocortin (POMC). Even though the study included only two patients with the disorder (POMC deficiency), they account for two-thirds of all known adult cases worldwide, according to Dr. Marc Reitman of the U.S. National Institute of Diabetes and Digestive and Kidney Diseases, HealthDay News reported.

Lack of MSH leads to the person being constantly hungry. “It’s like your body doesn’t know you’ve been fed, no matter how much you eat,” explained Reitman.

However, with the drug, the two patients showed a “dramatic alteration in their sensation of hunger, and their hyperphagia disappeared for the first time in their lives, leading to a normalization of their satiety,” said first author Dr. Peter Kuhnen, from the Charité–Universitätsmedizin, Berlin, Germany. There was no treatment alternative for such cases, he added.

The patients were both women in their 20s, weighing close to 350 pounds. Medical literature accounts for around 50 cases of POMC deficiency, according to the U.S. National Institutes of Health (NIH).

However, only three people are known to have survived the deficiency into adulthood.

According to a study published July 21 in the New England Journal of Medicine , researchers in France and Germany tested an experimental compound called setmelanotide on the two adults. The drug, developed by a Boston biotech firm called Rhythm Pharmaceuticals, activates a receptor on body cells that would normally be turned on by MSH, acting as a replacement for the hormone.

One of the two patients lost 112 pounds after 10 months of daily setmelanotide injections, while the other shed 45 pounds over just three months of treatment.

After stopping the first patient’s treatment after three months, the researchers found that she went back to being excessively hungry and started to regain the weight, according to Dr. Kuhnen.

Weight loss resumed once she went back on the drug, and “for this reason, we presume that the patients will need to take the drug indefinitely,” Kuhnen said.

However, the long term effects of the drug are yet to be studied. Kuhnen said the patients could develop resistance to the drug over time, requiring a dosage change at the very least.

High blood pressure is another concern but that has not been noted in the two patients, according to Reitman. MSH also stimulates a cell receptor in the skin and hair that has caused both women to experience a darkening of the skin and hair.

Rhythm Pharmaceuticals will also test setmelanotide in other genetic forms of obesity.

Another ongoing study is assessing patients with Prader Willi syndrome that reportedly affects an estimated one in 10,000 to 30,000 people worldwide. Reitman said the drug may also benefit people who are obese because they lack cell receptors for another appetite-curbing hormone called leptin, which accounts for up to 3 percent of people who become severely obese early in childhood, according to NIH.

“Relatively speaking, that's a common monogenic (single-gene) cause of obesity,” he said.

However, causes of common obesity are more complex and the study concentrates on the rarer varieties, like that associated with the POMC deficiency.