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New Fat-Loss Drug Resets Brain's Weight Setpoint
March 20, 2001 -- People who took an experimental obesity drug lost 10 pounds in 12 weeks -- and lost another pound even after they stopped treatment.
Animal studies have shown the drug works by resetting the brain's weight setpoint, essentially making a lower weight seem natural. Other weight loss drugs make the body feel as though it is starving -- and when treatment stops, animals respond by binge eating and rapid regain of weight. But even with access to all the food they wanted, overweight animals that received the new drug got thinner and stayed that way.
The drug, called Axokine, is a genetically engineered version of a natural brain chemical, called CNTF, that makes new brain cells grow. It is being developed by Regeneron Pharmaceuticals Inc. of Tarrytown, N.Y.
"[A] remarkable property that distinguishes ... weight loss [with CNTF treatment] from forced dieting is that [stopping] treatment does not result in binge overeating and immediate rebound weight gain," note Regeneron researchers Philip Lambert, PhD, and colleagues in the report published in the scientific journal Proceedings of the National Academy of Sciences. "This is apparently because of [its] ability to reduce food intake without triggering ... hunger signals and associated stress responses. [It] may alter, at least for a time, body weight settings encoded in the [brain]."
The Regeneron study team refused to speak directly with WebMD because of federal regulations that limit what a company's officers can say when it is about to make a public stock offering.
A human trial reported at a medical meeting last month showed that obese people who got the most effective dose of Axokine lost nearly 10 pounds over 12 weeks of treatment. Unlike previous weight loss drugs, these patients did not immediately regain the weight -- in fact, they lost another pound during the first six weeks they were off the drug, and they kept their lost weight off for a minimum of six weeks after discontinuing the medication. People who got fake injections gained about 1¾ pounds for the first 12 weeks and gained nearly 2 pounds more over the next 12 weeks.
A research pioneer in the field, Satya P. Kalra, MD, tells WebMD that the drug works a lot like leptin, a natural substance that tells the brain when the body doesn't need any more food. Leptin would make a great weight loss drug -- except that when a person becomes obese, he becomes resistant to it the same way a diabetic person becomes resistant to insulin. This new drug, however, works even in mice with the same kind of diet-induced leptin resistance that humans develop.
"This paper suggests they have produced a ... drug [that can reduce] body weight in situations where we know leptin is unable to act," Kalra tells WebMD. "They find [it] is very effective in bypassing leptin resistance. You are fooling nature, in a way, by presenting another molecule to the [brain] that activates the same signals as leptin."
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