NIH team reports breakthrough with new obesity drug

With an obesity epidemic raging in the U.S. and around the world, researchers have been delving into a new generation of compounds that help regulate metabolism. And one group of researchers at the NIH says they've made a key breakthrough in the field that could lead to new therapies that can help people safely shed pounds.

George Kunos, the scientific director of the National Institute on Alcohol Abuse and Alcoholism, was already familiar with studies pointing to the healthy effects of blocking endocannabinoids, the body's natural messengers which are chemically similar to the active compound in marijuana and help regulate a number of biological functions. Inhibiting endocannabinoids can trigger weight loss and help improve metabolism, cutting the risk of heart disease, diabetes and fatty liver. But the first generation of these drugs--which includes Acomplia, or rimonabant--also sometimes triggered anxiety, depression and suicidal thoughts once they hit the brain.

"Endocannabinoid receptors are present in the brain, as well as in peripheral tissues including the liver, skeletal muscles, pancreas and fatty tissues," explained Dr. Kunos, whose team included scientists inside as well as outside the NIH. "Activation of peripheral endocannabinoid receptors contributes to obesity-related metabolic and hormonal abnormalities."

So the researchers came up with a compound that was structured in a way that made it impossible to penetrate the brain, sticking with the endocannabinoid receptors in the tissue. The compound worked in obese mice, cutting 12 percent of their diet-induced weight. Mice that were administered rimonabant, which was never approved in the U.S. and had to be pulled from the European market, lost an average of 21 percent of their weight. The research team want to take their work another step to start along the road toward clinical trials.

Weight drugs have been a hot field in the biotech world. But the FDA advisory committee's recent vote against recommending Vivus' Qnexa has underscored the agency's unusually high safety standards for any new therapeutics targeting obesity.

- here's the NIH release
- here's the Reuters report

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