Peptides May Be Treatment Targets

The finding that the peptide hormones leptin, ghrelin, and the endocannabinoids are implicated in obesity and eating disorders (see Obesity and Eating Disorders: Are They Close Relatives?) is prompting some scientists to study whether these hormones, or compounds that act on them, might constitute effective new treatments for these conditions.

For example, researchers at Albany (N.Y.) Medical College discovered that injecting small fragments of leptin into subjects could control appetite, blood glucose levels, and weight gain. The drug can now be administered orally, using technology developed by Aegis Therapeutics. “The combination of Albany's highly effective peptide with Aegis' noninvasive ... peptide delivery technology promises to lead to the first orally active peptide anti-obesity and diabetes drug,” Edward Maggio, Ph.D., CEO of Aegis Therapeutics, reported at the annual meeting of the Endocrine Society in San Diego in June.

Rene Klinkby Stoving, M.D., Ph.D., an associate professor of endocrinology at Odense University in Denmark, and colleagues are conducting a pilot study to see whether an endocannabinoid receptor agonist, dronabinal, can increase weight and subdue motor restlessness in subjects with anorexia nervosa. The study is being funded by the U.S. National Institutes of Health.

However, no panaceas can be expected from such research.

One reason is that after leptin was discovered, there was great hope that administering it as a drug would be a treatment for obesity. It did lead to weight loss in obese people for a while, but eventually ceased to do so as they developed resistance to it.

Another reason concerns the endocannabinoid receptor antagonist rimonabant. It was approved by the European Union's regulatory agency in 2006 as an obesity treatment. Although it leads to modest weight loss, it can also cause some troublesome side effects, notably anxiety and depression.