Once that they had a docking receptor specific to white fat tissue, the researchers designed a drug. They created a synthetic ligand ” a sequence of amino acids that would fit neatly into the prohibitin receptor, like a key into a lock  ” and fused to it a corkscrew-shaped drug that they knew could induce a cell to self-destruct.

We have previously shown that this drug can be targeted to blood vessel cells of tumors of the prostate in mice, resulting in reabsorbtion of these tissues due to oxygen deficiency, says Pasqualini.

The ligand ” the guidance system ” brings the therapeutic drug to the prohibitin receptor, where it locks on, and then is internalized into the blood vessel cell, she says. It selectively destroys these blood vessels.

In a series of experiments, the investigators found that one month of treatment in severely obese mice was enough to restore the animal ™s normal body weight. None of the mice used in the therapy experiment were genetically altered or prone to obesity prior to treatment; they gained weight because they ate a high-fat diet.

The authors then conducted other experiments to make sure that the animals were not loosing weight because of nutrient malabsorption or appetite suppression. They note that there were no toxic side effects to the treatment and that the structure of the human prohibitin receptor is similar to the molecule found in mice.

But the authors caution that further studies are needed, especially to ensure that a drug that targets prohibitin receptors will not damage other vital tissues or vascular systems in the context of human disease and there is much more to be learned. Other collaborating investigators include Pradip Saha, Ph.D., an instructor in the laboratory of Lawrence Chan, M.D., a professor of medicine and molecular and cellular biology at Baylor College of Medicine.

Rapid loss of body fat in animals is often associated with undesirable side effects such as fat accumulation in the liver and in blood, says Chan. So we were pleasantly surprised that the treatment totally reversed the obesity without producing any of the usual complications.

The study was funded by the National Institutes of Health, as well as numerous foundation grants. Pasqualini and Arap say that they are planning a trial in obese non-human primates as a starting point for further validation and a stepping stone to trials in patients. mdanderson