A new compound has been shown to reduce Body Mass Index (BMI) and abdominal circumference in obese rhesus monkeys, and imaging revealed a substantial decrease in body fat. In contrast to current ‘drugs’ for obesity that control appetite or absorption of dietary fat, this experimental drug binds to a protein on fat-supporting blood vessels and, once there, triggers cell death.
Rhesus monkey (or Macaca mulatta)
(Source: Wikimedia Commons, user Einar Fredriksen)
The same compound (named Adipotide, formula: CKGGRAKDC-GG-D(KLAKLAK)2) was tested in mice earlier, where it resulted in a 30 percent loss of body weight. Important to note is that the test animals were obese. Separate tests on lean colleague primates showed that these did not lose any weight, since the drug acts on the so-called white fat (the unhealthy kind). The obese rhesus monkeys lost about 27% of abdominal fat and they remained bright and alert, interacting with care-givers and showing no signs of nausea or food avoidance.
The only side effects to be noted were “predictable and reversible changes in renal proximal tubule function.” The treated monkeys also showed significant improvements in insulin-resistance. Due to the great results, and the manageable side-effects, the authors are preparing a human trial on obese prostate cancer patients. The reason for this is that some prostate cancer treatments, such as hormones, can cause weight gain, which in turn, can lead to arthritis (which may result in more weight gain, a vicious cycle), type 2 diabetes and cardiovascular problems.
In the primate test subjects, the effects of the drug lasted up until three weeks after administration. During the fourth week, a slow reversal could be noticed.
The researchers conclude:
Treatment with adipotide induced targeted apoptosis within blood vessels of white adipose tissue and resulted in rapid weight loss and improved insulin resistance in obese monkeys. Magnetic resonance imaging and dual-energy x-ray absorptiometry confirmed a marked reduction in white adipose tissue. At experimentally determined optimal doses, monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function. Together, these data in primates establish adipotide as a prototype in a new class of candidate drugs that may be useful for treating obesity in humans.
Barnhart, K.F.; Christianson, D.R.; Hanley, P.W.; Driessen, W.H.P.; Bernaky, B.J.; Baze, W.B.; Wen, S.; Tan, M.; Ma, J.; Kolonin, M.G.; Saha, P.K.; Do, K.-A.; Hulvat, J.F.; Gelovani, J.G.; Chan, L.; Arap, W. and Pasqualini, R. (2011). A Peptidomimetic Targeting White Fat Causes Weight Loss and Improved Insulin Resistance in Obese Monkeys. Science Translational Medicine. 3(108). Published online 9 November. doi:10.1126/scitranslmed.3002621.
The University of Texas, MD Anderson Cancer Center, News Releases.