(The New York Times News Service) - If Maria Rupnick turns out to be right, losing weight may one day become unprecedentedly easy for millions of obese people.

In laboratory experiments at MIT and the Children's Hospital in Boston, Rupnick has shown that an entire class of compounds designed to inhibit cancer may also, without any obvious side effects, cause extraordinary weight loss.

So far Rupnick, now a researcher and instructor at Brigham & Women's Hospital in Boston and at Harvard Medical School, has conducted her experiments only in mice - especially so-called ob/ob mice, which are very fat creatures naturally predisposed to eating constantly and thus weighing two to three times as much as a normal mouse.

It could be a long time before her theory is tested in humans. Indeed, Rupnick has not yet even published her findings, which she submitted in November to a scientific journal where they are currently under peer review.

Already though, Rupnick, who is 39, has received a Young Investigators award from the American Heart Association for her work. And in October she received U.S. patent 6,306,819, which covers the commercial applications of her work.

Among Rupnick's mentors are two maverick investigators, Judah Folkman and Robert S. Langer. As a postdoctoral student she worked in the laboratory of Folkman, the surgeon and cancer researcher at Harvard, who for decades bucked conventional medical wisdom by theorizing that tumors were able to grow beyond a certain size because they could create their own blood vessels.

Folkman was the first to create an angiogenesis inhibitor - a drug designed to shrink tumors by cutting off their blood supply. More than a score of angiogenesis inhibitors are currently in clinical trials and these drugs now are considered among the most promising in cancer research.

About three years ago, Rupnick started to wonder whether the inhibitors might also have an effect on fat. But when she reviewed scientific literature on the subject she did not find much.

But for Rupnick, fat was fascinating. "In an adult, whether it's a human or a mammal, we have all of the blood vessels we need," she said. "Unless there is injury or pregnancy, no new blood vessels are created. The highway is already built."

Except in the case of fat. "Adipose tissue" - i.e., fat - "is a noncancerous normal tissue that unlike any other tissue in the body can grow and regress, grow and regress rapidly and substantially depending on caloric intake," Rupnick said.

As Rupnick remembers it, Folkman was not initially enthusiastic about her proposal to study the vascular structure of fat - nor was anyone else. "The conservative response," she recalled, "was, "What, are you crazy? You'll never be able to get funding. No one will ever publish your work.' There are just so many charlatan things associated with the market."

The climate at the time, 1998, was certainly not propitious. Fen-phen, a popular diet drug combination had recently been pulled from the market because it was suspected of causing heart valve damage. Moreover, Folkman was involved in a controversy after outside scientists initially were unable to replicate his success in treating mice tumors by attacking the tumors' blood supply. He understandably "had concerns about the publicity" that her research might generate, Rupnick said. (In early 1999, scientists at the National Cancer Institute said they were able to confirm Folkman's results.)

Despite the reservations of her colleagues at Harvard, Rupnick said Langer, an investigator at MIT who specializes in tissue engineering, was intrigued by her fat investigations. "Bob Langer comes from MIT, which has a very different perspective," she said. "It translates and deals with business much more than the medical school does."

Rupnick tested five different angiogenesis inhibitors, including TNP-470, angiostatin and endostatin, on ob/ob mice and other obese mice.

The most surprising thing was that not only did the mice stop gaining weight, they also lost a significant amount of weight.

Depending on the dose, "we decreased their body weight by almost half - that's enormous," Rupnick said. The drugs were working far better than any approved obesity drug ever had, she said.

The first reaction she got from obesity experts was that the drugs must be toxic. But Rupnick said that at normal dosages so far she had found no evidence of toxicity in the mice. And while the fat tissue shrinks, nothing else appears to - not the brain, the heart, the liver, or any other organ. Nor did the mice seem to be developing diabetes or any other chronic disease.

Why did they lose so much weight? Rupnick's theory is that the mice - whose appetites decreased significantly while on the drugs - were using the fat as fuel.

"If that fat goes into their blood stream - which is where it has to go because it has to go somewhere - it gets converted into fatty acids and other things that can be used as a fuel," she said. So the animal essentially consumes its own fat for energy.

"I don't think that it's toxic at all," said Rupnick, who noted nonetheless that it would be impossible to prove that any drug was 100 percent nontoxic. (Angiogenesis inhibitors, however, can interfere with wound healing and menstruation or pregnancy.)

Rupnick's work suggests that blood vessels in fat never seem to fully mature but they instead exist in a special environment that allows them to grow or retract depending upon the caloric needs of the organism. This could have much larger implications. Rupnick, who is trained as a cardiologist, imagines that one day perhaps blood vessels in organs like the heart might be coaxed back into their immature state and made to heal themselves.

In the meantime, MIT and the Children's Hospital have licensed Rupnick's patent, with Langer and Folkman listed as co-inventors, to Repair Inc., a Boston company.

Copyright 2002 The New York Times News Service. All rights reserved.