According a new study an experimental anti-cancer drug could help fight obesity. The drug chokes off the blood supply to fat cells and helped obese monkeys slim down in the experiments.
The drug called Adipotide, takes a different approach from other weight loss medicines, which have generally tried to control appetite, alter the absorption of fat or increase metabolism in order to help people lose weight.
“Development of this compound for human use would provide a non-surgical way to actually reduce accumulated white fat,” said Renata Pasqualini of University of Texas MD Anderson Cancer Center, whose study appears in the journal Science Translational Medicine. Pasqualini explained that the drug acts by seeking out and sticking to proteins on the surface of blood vessels that feed white fat cells - the kind that gathers under the skin and around the middle. Once attached, the drug releases a synthetic molecule that triggers a natural process of cell death that kills the fat cells.
Earlier tests of the drug on obese mice helped them lose 30 percent of their body weight. The new experiments involved 15 monkeys that became obese in much the same way humans do - by overeating and getting too little exercise.
Ten monkeys were treated and five were the control group. At the end of the study, treated monkeys lost an average of 38.7 percent of their total body fat, compared to 14.8 percent for the control animals. Treated monkeys also lost 27 percent of their abdominal fat.
Monkeys remained bright and alert throughout the study. The chief side effects were increased urine output and slight dehydration, both symptoms of mild kidney failure. But these were reversible and varied by dose. The researchers are now planning to test the drug in obese patients being treated for prostate cancer.
The researchers' 2004 paper showing a 30% weight loss in obese mice drew skepticism. Randy J. Seeley, director of the diabetes and obesity center at the University of Cincinnati, figured destroying white fat cells would make animals and people sick. But his own lab eventually replicated the mouse study, using rats instead, and now he is intrigued. “This is really new stuff,” Dr. Seeley said of the latest results. “There's no way to know if this will become a therapy or not, but at least it opens up a new way to think about therapies, and we have not had a lot of those.” He isn't involved with the research.
“Obesity is a major risk factor for developing cancer, roughly the equivalent of tobacco use, and both are potentially reversible” Dr. Wadih Arap, also of MD Anderson, who worked on the study, said in a statement.
“Obese cancer patients do worse in surgery, with radiation or on chemotherapy - worse by any measure.” Patients in the study will get daily injections of the drug for 28 consecutive days. “The question is, will their prostate cancer become better if we can reduce their body weight and the associated health risks,” Arap said.
James Hulvat, head of research and development for Ablaris Therapeutics, said the decision to test the agent first in obese prostate-cancer patients partly reflects the interests of M.D. Anderson, which is funding the initial study. The company also hopes to find an early benefit for the drug in a limited group of patients. “We'll carry the drug forward into a broader weight-loss indication if the [initial] clinical trial data support that,” he said. The company is also interested in pursuing the agent as a potential treatment for type 2 diabetes, which is associated with obesity.
“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. Cao also stressed that the gap between monkeys and humans is “a big jump.” “Whether this will reach the clinic remains to be seen,” he said.
At present there are no safe and effective weight lowering drugs. However more than a third of Americans are overweight and more than a quarter are obese, increasing their chances of developing health problems including type 2 diabetes, heart disease, high blood pressure, fatty liver disease and some cancers. The new study was funded by the National Institutes of Health and various philanthropic foundations.
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