An experimental drug developed from cancer research showed early promise in a study of weight loss, researchers report, causing fat monkeys to shed an average 11% of their body weight after just a month of treatment.
Rhesus macaques injected daily with the drug, called adipotide, also dropped 39% of their fat deposits, slimming their bellies, and showed improvement in metabolic functions including insulin resistance, a risk factor for Type 2 diabetes.
How does the new drug work? By stemming the blood flow to fat cells and killing them off. The mechanism is borrowed from a cancer treatment strategy called angiogenesis inhibition, which starves tumors of their blood supply the same way; it’s the basis for several drugs that are used to treat cancers of the brain, colon, lungs and kidneys.
Although the obesity study is preliminary — just a proof of concept — it is an interesting advance, particularly in light of the difficulty researchers and regulators have faced in finding a safe, long-term obesity drug. Six prescription medications for weight loss are currently approved by the Food and Drug Administration, and only one of them — orlistat — is considered appropriate for long-term use (the once-popular Meridia was withdrawn in 2010 because of heart risks). Until now, most weight loss medications have focused on suppressing appetite or revving up metabolism — with disappointing results. “Targeting blood vessels of white fat tissue is a novel conceptual approach against obesity,” study author Dr. Wadih Arap, professor of medicine at M.D. Anderson Cancer Center, in Houston, told HealthDay.
Arap and his wife, Dr. Renata Pasqulini, who is also a cancer researcher at M.D. Anderson, developed the treatment together. In 2004, they published a paper showing that the drug produced a 30% weight loss in mice. Since then, other scientists have replicated the finding in rats. Now a human trial, involving advanced prostate cancer patients, may begin early next year.
It’s still not clear exactly how adipotide causes weight loss, or whether the results in animals will translate neatly to humans. Also, the drug produced some side effects in the monkeys, including dehydration and some mild changes to the kidneys. The symptoms disappeared after treatment was stopped, but they could be problematic if the drug is to be used in humans long term.
The company that Arap and Pasqualini founded, Ablaris Therapeutics — a subsidiary of Arrowhead Research Corp., with which M.D. Anderson has partnered to develop the drug further — is now working to reduce the side effects and to come up with a version of adipotide that wouldn’t have to be injected as frequently, according to the Los Angeles Times.
The Times’ Melissa Healy reported:
“This is exciting and very interesting work,” said Yihai Cao, a microbiologist at the Karolinska Institute in Sweden who studies angiogenesis in tumors. But, he added, the researchers will need to clearly show that adipotide is reducing blood vessels that nourish fat without harming other blood vessels, as well as how appetite changes and metabolic improvements are related to that effect.
The new study was published in Science Translational Medicine.