Obese Monkeys Lose Weight as Drug Targets Blood Vessels in Fat

Obese rhesus monkeys lost an average of 11 percent of their body weight on an experimental drug that cut off the blood supply to fat tissue, raising the possibility the treatment may work in humans, researchers said.

The medicine, dubbed Adipotide by developer Ablaris Therapeutics Inc., also enabled the monkeys to use about 50 percent less insulin to keep blood sugar levels down and prevent damage to internal organs. The study was published in the journal Science Translational Medicine today.

At least 20 percent of adults are obese in every state in the U.S., according to the U.S. Centers for Disease Control and Prevention. The monkeys had become obese through a lack of physical activity and too much food, just as humans do. Obesity has been linked to diabetes, heart attacks and certain kinds of cancer, including breast, colon and kidney cancers.

“Obesity is a major risk factor for developing cancer, roughly the equivalent of tobacco use, and both are potentially reversible,” said study coauthor Wadih Arap, a professor of medicine at MD Anderson’s David H. Koch Center for Applied Research of Genitourinary Cancers in Houston, in a statement.

The researchers next will test the medicine in obese prostate cancer patients, who frequently gain weight in response to treatment.

Closely held Ablaris is based in Pasadena, California.

Injecting Monkeys

The monkeys were injected with the drug every day for four weeks. They didn’t show signs of nausea and remained alert throughout the treatment, the scientists said. A study in lean monkeys showed no effect on their weight, suggesting the therapy may only work in obese subjects.

Blood vessels have different kinds of proteins on their surfaces depending on where they are on the body, according to the study. The drug targets a protein called prohibitin that is unusually common in vessels in fat tissue. Killing the protein destroys the vessel, prompting the body to metabolize the fat and lose weight.

Two weight-loss medicines are approved by the U.S. Food and Drug Administration, the generic phentermine, and orlistat, marketed in the U.S. by London-based GlaxoSmithKline Plc as Alli over-the-counter, and as Switzerland-based Roche Holding AG’s Xenical by prescription. Neither works in a way similar to the Ablaris therapy.

Other drugs targeting weight loss, including Abbott Laboratories’ Meridia, have been withdrawn due to side effects.

Obesity Competition

Three experimental medicines are competing to be the first obesity drug approved by U.S. regulators in more than a decade. La Jolla, California-based Orexigen Therapeutics Inc. said in September that it reached an agreement with the FDA and would start a two-year trial with fewer than 10,000 patients to study the drug’s heart risks.

In October, Vivus Inc., based in Mountain View, California, resubmitted drug Qnexa with more information about birth defects, after having been rejected by the FDA last year. San Diego-based Arena Pharmaceuticals Inc.’s drug was rebuffed by U.S. regulators last year, with the agency requesting more data about a brain tumor risk seen in rats.

Obesity is defined as having a body mass index above 30. A 6-foot-tall adult man weighing 221 pounds (100 kilograms) or more is considered obese, as is an adult woman standing 5 feet, 6 inches tall weighing 186 pounds or more, according to the U.S. National Institutes of Health.

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