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Drug Leads to Weight Loss in Obese Monkeys

Conquest - Spring 2012

Kirstin Barnhart, D.V.M., works with rhesus monkeys to study the efficacy of a new 
weight-loss drug.
Photo: Houston Chronicle

Clinical trial for obese prostate cancer patients coming

By Scott Merville

Obese rhesus monkeys treated with an experimental drug that starves fat cells by destroying their blood supply lost, on average, 11% of their body weight in four weeks.

Treatment also slimmed the monkeys’ waistlines, reduced their body mass index (BMI) and decreased body fat. All measurements were unchanged in untreated monkeys.

“Development of this compound for human use could provide a nonsurgical way to actually reduce accumulated fat, in contrast to current weight-loss drugs that attempt to control appetite or prevent absorption of dietary fat,” says co-senior author Renata Pasqualini, Ph.D., professor in MD Anderson’s David H. Koch Center for Applied Research of Genitourinary Cancer.

Most drugs developed to treat obesity focus on suppressing appetite or increasing metabolism, but both approaches have been thwarted by toxic side effects.

The MD Anderson group designed a new drug, Adipotide™. It includes a homing component that binds to a protein on the surface of fat-supporting blood vessels and a synthetic peptide that triggers cell death. With their blood supply gone, fat cells die and metabolize.

Obesity raises cancer risk, worsens treatment outcomes

“Obesity is a major risk factor for developing cancer, roughly the equivalent of tobacco use, and both are potentially reversible,” says co-senior author Wadih Arap, M.D., Ph.D., professor in the Koch Center. “Obese cancer patients do worse in surgery, with radiation or on chemotherapy — worse by any measure.”

The monkeys in the study were “spontaneously” obese, says Kirstin Barnhart, D.V.M., Ph.D., assistant professor in MD Anderson’s Department of Veterinary Sciences and veterinary clinical pathologist at MD Anderson’s Keeling Center for Comparative Medicine and Research in Bastrop, Texas. Nothing was done to make them overweight. They did it the way humans do, by eating too much and avoiding physical activity.

The researchers are preparing a clinical trial in which obese prostate cancer patients would receive daily injections of Adipotide for 28 days. “The question is: Will their prostate cancer be affected if we can reduce their body weight and the associated health risks?” Arap says.

The monkeys regained their lost weight after treatment ended, suggesting that the best general use of the drug, if it proves effective in humans, might be to jump-start a weight-loss program.

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