Researchers announce marked success with a new weight loss drug in a primate study using obese rhesus monkeys that lost on average 11 percent of their body weight with a new drug called Adipotide. Past weight loss drugs have focused on either curbing appetite or increasing a person’s metabolism, but have met with little success toward weight loss. With Adipotide, weight loss is achieved by targeting the blood vessels that feed white fat cells. The researchers’ weight loss drug success in primates has opened the door to clinical trials in man.
When an individual has a body mass index (BMI) of 30 or higher, he or she meets the medical requirement for a diagnosis of obesity. Obesity has serious consequences, some of which include an increased risk of cardiovascular disease, diabetes and other disorders associated with metabolic syndrome. Researchers of a recent weight loss drug study at the University of Texas MD Anderson Cancer Center, however, point out that obesity also plays a significant health risk in individuals with cancer. Co-author Wadih Arap, M.D., Ph.D. states that, “Obesity is a major risk factor for developing cancer, roughly the equivalent of tobacco use, and both are potentially reversible…obese cancer patients do worse in surgery, with radiation or on chemotherapy— worse by any measure.”
Dr. Wadih and colleagues have designed a new weight loss drug that differs from previous weight loss drugs, which focused on either suppressing appetite to reduce food consumption or increasing a person’s metabolism to burn off more calories. Their drug is designed to target a specific protein that is on the surface of blood vessels that feeds fat cells. Not only does the drug target the blood vessels to the fat cells, but it also delivers an artificial protein that signals the cells of the blood vessels to self-destruct. When the blood vessel cells self-destruct, the fat cells are then deprived of blood, which causes the fat cells to then die and be reabsorbed by the body.
In the study, rhesus monkeys that were naturally obese due to over-eating and avoidant of physical activity, were given the weight loss drug and compared to control obese rhesus monkeys that were not given the drug. Rhesus monkeys were chosen as the experimental animal because rodent studies have demonstrated that man and mouse are too far removed genetically and physiologically to test the true effectiveness of the drug. Primate models are preferred because they share many conditions of obesity with man such as resistance to insulin, Type 2 diabetes and cardiovascular disease.
The results of the study demonstrated a marked improvement in the health of the obese rhesus monkeys that were given the weight loss drug. On average, there was an overall rapid weight loss of 11 percent within four weeks of treatment. Furthermore, not only did the BMI of the treated obese primates reduce, but the fat that had accumulated around their waistlines prior to the treatment was also significantly reduced. Abdominal fat is of particular importance because unnaturally large fat deposits in the abdomen surrounding the organs is strongly correlated with metabolic disease as opposed to fat deposits that are spread more evenly throughout the body.
The untreated obese control primates did not lose weight and in some cases continued to gain weight during the study. In addition, in a separate study to determine the effect of the weight loss drug on relatively lean rhesus monkeys, weight loss did not occur with treatment, which indicates that the weight loss drug is likely selective for treating obese primates only.
Another added benefit of the weight loss treatment on the obese rhesus monkeys was a decrease of approximately 50 percent in the number of insulin injections needed for treating the obese monkeys in the study that have insulin resistance.
The only reported side effect was the development of some renal problems in the kidneys that proved to be dose-dependent and treatable. Clinical trials are underway to test the weight loss drug success on obese prostate cancer patients. The obese patients will receive daily injections of the weight loss drug Adipotide for a month. “The question is, will their prostate cancer become better if we can reduce their body weight and the associated health risks,” says Dr. Arap.
Source: Science Translational Medicine, 2011; 3 (108): 108ra112 DOI: 10.1126/scitranslmed.3002621