New obesity compound shows promise in mice

CHICAGO (Reuters) - A compound similar to Sanofi-Aventis’ once-promising weight loss drug Acomplia helped obese mice lose weight and lower their blood fats and blood sugar without causing psychological side effects, U.S. researchers said on Monday.

Like Acomplia, the drug targets cannabinoid receptors that become active after smoking marijuana, but the team tinkered with the compound to keep it from crossing over into the brain, reducing the risk of depression, anxiety or other neurological problems seen in the original drug.

While obese mice do not lose as much weight on this new compound, it was just as effective as Acomplia in reducing obesity-related metabolic changes, researchers from the National Institutes of Health and Northeastern University reported in the Journal of Clinical Investigation.

“It does cause weight loss in diet-related obesity, but less than the other compound, which is not the only problem in obesity,” Dr. George Kunos of the NIH in Bethesda, Maryland, said in a telephone interview.

Obesity has become an epidemic in the United States, leading to a huge increase in diabetes and a host of related health problems. But many potential weight-loss drugs have either failed or been abandoned due to safety issues.

Acomplia had to be pulled from the market after it was linked to several deaths and hundreds of adverse drug reactions in Britain.

The drug, known generically as rimonabant, never won U.S. approval after a panel of experts rejected it amid fears it may cause suicidal thoughts.

Rimonabant targets the protein CB1R, the same molecule that controls the effects of marijuana. CB1R is present both in the brain and in organs such as the liver and pancreas and fat tissue.

Kunos and Alexandros Makriyannis of Northeastern University in Boston tested a more selective drug that only blocks CB1R in peripheral organs, but cannot get into the brain.

They found mice that become fat from eating too much lost about 12 percent of their body weight on this new formulation, compared with 21 percent in similar mice that had taken rimonabant.

But Kunos said the other effects -- reduced blood fats that can cause heart disease and lower blood sugar that can affect the risk of diabetes -- were about the same with both the new and the old drugs.

Kunos said the drug had no effect on mutant mice that were obese because they lacked the appetite-suppressing hormone leptin.

“In obesity, mice and humans lose their sensitivity to leptin. This drug restores that sensitivity,” Kunos said, offering a possible explanation for the difference.

He said the next step is to do tests to see if the drug is toxic to humans. Eventually, the hope is that the drug will be tested as a new anti-obesity treatment.

Editing by Mohammad Zargham