A shot at fighting fat
Biotech company testing therapy in a syringe - a vaccine designed to prevent feeling of hunger




BY RONI RABIN
STAFF WRITER

May 14, 2005

For overweight people who've tried pills, protein diets and personal trainers, a new weight loss therapy may be on the horizon - in a syringe.

A Swiss biotechnology company is enrolling 112 obese volunteers in the first human trial of a vaccine designed to trigger antibodies to ghrelin, a human peptide, or hormone, that stimulates the appetite.

The volunteers, who must live in Switzerland and have a body mass index of between 30 and 35, will receive monthly shots for six months. A control group will receive placebo injections, and all will be counseled on diet and exercise.

"The vaccination aims to induce antibodies against ghrelin that will bind the ghrelin in the blood system, so it does not get to the brain and cannot induce a feeling of hunger," said Claudine Blaser, director of corporate communications for Cytos Biotechnology, the Zurich company doing the trials.

But, she said, behavioral change is essential as well.

Cytos is competing with other companies seeking to develop ghrelin antagonist pills. Other hormones, such as leptin, which suppresses appetite, are also the focus of research.

Levels of ghrelin, a chemical messenger identified in 1999, increase before a meal and decrease after eating. The peptide also seems to play a role in long-term weight regulation. After weight loss occurs, blood levels of ghrelin rise dramatically, which may explain why so many dieters quickly regain the pounds they managed to lose. Still, it is not entirely clear that blocking ghrelin's action will lead to weight loss. Most obese people have low levels of ghrelin, said Dr. David Cummings, an associate professor of medicine at University of Washington in Seattle who has studied ghrelin extensively.

"If it's already low in people who are obese, then further lowering it may not help," Cummings said. Suppressing ghrelin activity may be most effective after a diet, he said, when it might prevent the yo-yo dieting syndrome in which people quickly regain weight.

"Ghrelin is not the underlying molecular cause of obesity," said Cummings, who is a consultant to Abbott Laboratories. "We haven't figured out the underlying cause yet."

If the vaccine under development, CYT009-GhrQb, works, it will trigger development of antibodies that bind with ghrelin in the blood and reduce ghrelin uptake into the brain, where it triggers eating.

When the vaccine was administered in mice, the mice developed antibodies to ghrelin, and when fed a high-fat diet, they gained 15 percent less weight than unvaccinated mice.

Dr. Marc Jacobson, a childhood obesity expert at Long Island Jewish Medical Center, said suppressing ghrelin's appetite stimulating effect was unlikely to be an obesity cure-all.

"Ghrelin is one of maybe 10 or 12 different hormones that regulate our weight. ... Even if a vaccine wipes out this particular hormone's effect, there might be others that reverse any effect you would get."
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