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New Drug May Treat Rare Obesity Disorder Causing Constant Hunger

👤by Amy Norton 0 comments 🕔Thursday, July 21st, 2016

WEDNESDAY, July 20, 2016 (HealthDay News) -- An experimental drug spurred substantial weight loss in people with a rare genetic disorder that causes severe obesity because patients feel perpetually hungry.

The study included only two patients with the disorder, known as proopiomelanocortin deficiency.

But those two patients account for two-thirds of all known adult cases worldwide, said Dr. Marc Reitman, of the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

The disorder is caused by mutations in the gene that makes the protein called proopiomelanocortin (POMC).

Normally, the POMC protein gets chopped into smaller proteins that affect different hormones in the body, explained Reitman, who wrote an editorial published with the study.

When the body lacks POMC, the adrenal glands (which churn out vital hormones) cannot work properly. If that adrenal insufficiency isn't recognized and treated quickly, the disease kills in infancy.

Around 50 cases of POMC deficiency have been reported in the medical literature, according to the U.S. National Institutes of Health (NIH).

But only three people are known to have survived into adulthood, Reitman added.

Those survivors have revealed another consequence of POMC deficiency: extreme obesity. And that, research has shown, seems to stem from a lack of another hormone derived from POMC -- called melanocyte-stimulating hormone (MSH).

Without MSH, people are constantly hungry. "It's like your body doesn't know you've been fed, no matter how much you eat," Reitman said.

The standard way to treat any hormone deficiency is to replace the hormone. But until now, there has been no good replacement for MSH.

In the new study, researchers in France and Germany tested an experimental compound called setmelanotide in two adults with POMC deficiency.

The drug is being developed by a Boston biotech firm called Rhythm Pharmaceuticals, to treat rare genetic causes of obesity.

According to the company, setmelanotide activates a receptor on body cells that would normally be turned on by MSH. So it essentially acts as a replacement for MSH, Reitman explained.

The patients in this study -- both women in their 20s -- were severely obese, weighing close to 350 pounds.

After about 10 months of daily setmelanotide injections, one patient had lost 112 pounds. The other dropped 45 pounds over three months of treatment.

The first patient initially had her treatment stopped after three months. She immediately became excessively hungry and began to regain the weight, said lead researcher Dr. Peter Kuhnen.

Once the patient went back on the drug, her hunger eased and her weight loss continued, the researchers said.

"For this reason, we presume that the patients will need to take the drug indefinitely," said Kuhnen, who is based at Charite-Medical University of Berlin, in Germany.

No one can predict how the patients will fare in the long term.

In theory, Kuhnen said, they could develop resistance to the drug, and at least need a dosage change.

Reitman said there's also some concern that the drug could cause high blood pressure.

But that has not happened yet in these patients. And one woman saw her blood pressure go down -- probably because of the large weight loss, according to Reitman.

One side effect was seen in both women: Their skin and hair darkened.

That's not surprising, Reitman said, because MSH stimulates another cell receptor in the skin and hair. (Lacking MSH, people with POMC deficiency have pale skin and red hair.)

According to Rhythm Pharmaceuticals, which provided the drugs for the study, setmelanotide will be tested in other genetic forms of obesity.

An ongoing study is looking at patients with Prader Willi syndrome -- which affects an estimated one in 10,000 to 30,000 people worldwide, according to the NIH.

The genetics of Prader Willi are complex. But patients' obesity is thought to involve the same molecular "pathway" seen in POMC deficiency, Kuhnen said.

Reitman speculated that the drug might benefit people who are obese because they lack cell receptors for leptin -- an appetite-curbing hormone.

"Relatively speaking, that's a common monogenic [single-gene] cause of obesity," he said.

By NIH estimates, leptin receptor deficiency may account for up to 3 percent of people who become severely obese early in childhood.

What's not clear is whether the findings have any relevance for the millions of people with "garden-variety" obesity, Reitman said.

It's possible there is an issue with "MSH signaling" in some cases of common obesity, he said.

But he also pointed to the complexity of common obesity: For one, even though there's a genetic component, many different genes have been linked to obesity risk.

The study was published July 21 in the New England Journal of Medicine.

Article Credits / Source

Amy Norton / HealthDay

Amy Norton wrote this story for HealthDay. HealthDay provides up to the minute breaking health news. Click here to view this full article from HealthDay.

SOURCES: Peter Kuhnen, M.D., Institute for Experimental Pediatric Endocrinology, Charite - Medical University of Berlin, Germany; Marc Reitman, M.D., Ph.D., chief, diabetes, endocrinology and obesity branch, U.S. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md.; July 21, 2016, New England Journal of Medicine

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