New hope for failed obesity drug

NEW YORK - Leptin, the appetite-suppressing drug that flunked tests for weight loss in people, is resurrecting hope with a study showing it worked better in mice when combined with other medicines.

The research showed obese mice lost weight when given a combination of leptin and either a generic liver drug or a second medicine used for enzyme deficiencies. Amylin Pharmaceuticals Inc. of San Diego, which acquired rights to leptin in 2006, wasn't involved in the study, performed at Harvard University and the University of Michigan.

Leptin, a hormone, generated hope 10 years ago that it would be an effective treatment for obesity, and never delivered benefits because many people develop a resistance to the hormone in the brain. The findings in the journal Cell Metabolism show a way researchers may be able to overcome that resistance, allowing obese people to control appetite and lose weight, the researchers said.

"We believe that we've identified the core mechanism that causes leptin resistance," said the study's senior author, Umut Ozcan, an endocrinologist at the Harvard-affiliated Children's Hospital Boston, in a telephone interview. "If this works in humans, it may create a new treatment plan for obese humans."

About two-thirds of US adults are overweight or obese, and obesity is the number two cause of preventable premature death in the nation, behind smoking.

Leptin, discovered in 1994, is a natural hormone made by fat cells. When more fat is stored in the body, leptin rises, signaling to the brain that the body has had enough to eat. Earlier studies of leptin found binge-eating mice that lacked leptin lost weight when given the hormone. When obese people took leptin, patients didn't benefit, because they already had elevated levels of the hormone.

Amylin acquired the rights to leptin for an undisclosed amount in 2006 from Amgen Inc. of Thousand Oaks, Calif. Amylin has pursued a different line of research on leptin and is in the second of three phases of human testing of the hormone in combination with another drug, pramlintide, the active ingredient in its diabetes drug Symlin.