Designer Weight-Loss Drugs on Horizon
New Compound Switches Off Appetite, Boosts Fat-Burning
By Daniel DeNoon
WebMD Medical News Reviewed By Gary Vogin, MD
June 10, 2002 -- An experimental drug that makes fat mice thin points the way to designer weight-loss drugs.
It's called C75. In mouse studies, it reduces appetite and makes the body burn fat faster. That's supposed to be impossible. Millions of years of evolution have hard-wired animals to save their energy during lean times. It's the bane of the eat-less diet: you burn off fat more slowly when you are losing weight. C75 somehow short-circuits this system.
Now scientists know why. And that knowledge seems likely to lead to designer drugs that can help people control their appetite while melting away stored-up fat. The new findings appear in the June 11 issue of Proceedings of the National Academy of Sciences.
"C75 is the one molecule that goes between making fat and burning it," study leader Frank Kuhajda, MD, tells WebMD. "We are mucking with the switch. Now we have an explanation of why these animals lose so much weight."
And lose weight they do. Kuhajda and colleagues at Baltimore's Johns Hopkins University saw obese mice lose 15% of their body weight after only two weeks on C75. Oh, yes, and there's one more thing about it: C75 also kills cancer cells.
But don't run out to the pharmacy looking for the drug. It's years away from any kind of human trial. Kuhajda says that even if C75 were safe in humans -- a very, very big "if" -- it isn't the right kind of drug for people.
"We can take a clue from this work to design molecules that might be drugs in the future," he says. "C75 will never be a weight-loss or cancer drug. But it is a useful tool. This work shows you how to do it."
When an animal stops eating, a kind of fatty acid builds up in the system. It's like when an assembly line shuts down. Raw materials pile up at the front end. This fatty-acid buildup signals the body to slow energy burning. C75 acts on the brain to make an animal lose its appetite. It also acts on the body to block the signals coming from fatty acids. It keeps the fat-burning machinery running at full blast
It would be dangerous for people to lose weight at the same speed as Kuhajda's mice. That's why he's looking for other drugs that would give doctors better control of the appetite and fat-burning systems.
"What we are trying to do is tip the balance between slowly gaining weight and slowly losing weight," Kuhajda says. "We are not trying to make beautiful people. We are trying to help people, like diabetics, lose maybe 15 or 20 pounds. What I see is a C75-like drug in the future that makes you a little less hungry and makes you burn a little more fat. You don't have to crash and go into starvation. What we want is for you to eat a little less and to burn a little more fat every day. Maybe at the end you are still a little chunky, but your health is better. This is early, but so far it looks promising."
C75 is no magic bullet, agrees Jules Hirsch, MD, director of the Laboratory of Human Behavior and Metabolism at New York's Rockefeller University. Hirsch, a long-time expert in the field, sees the new findings as one more milestone in the search for new obesity treatments.
"If you take in more calories than you burn, you gain weight. It is an equation that is a basic law of science. There is no way around that," Hirsch tells WebMD. "What I am hoping for is a much greater understanding of how this whole food intake mechanism is set up. If we have that, maybe we will have better ways of treating obesity in the first instance, whether it starts in childhood or later."