Link:
http://www.starbanne...1017/FEATURES01Date: 11-10-03
Author: -
Source: New York Times
The Drug Industry's Holy GrailPublished November 10. 2003 8:30AMNew York TimesIf the drug industry has a commercial Holy Grail, it might be an anti-aging pill, one that would let you live longer and prolong your youthful vigor. The market would be huge, of course. The problem is that to get it approved by the Food and Drug Administration, researchers would have to find a way to demonstrate that it works. To prove it was safe and effective, a company would have to give it to people and then wait to see if they lived longer than a control group that did not take the drug. The researchers might have to wait decades, by which time their patent protection rights 17 years, by current law would be long gone. The company would pay the costs of research and development, and the generic drug industry would reap the benefits.
"It's a bear of a problem," said Dr. Leonard P. Guarente, a biology professor at the Massachusetts Institute of Technology and a founder of Elixir Pharmaceuticals, which, according to its Web site, seeks "therapeutics that slow aging, forestall the disease and disability that accompany aging, and extend life's most productive period."
The company is pinning its hopes on a gene that is turned on with very low-calorie diets. This gene's activity, Dr. Guarente said, is the reason such a diet, if someone could stand it, might prolong life.
The company's aim is to find a drug that will turn up the activity of the gene, SIRT1, giving the effect of a diet without having to be on one.
But then what?
One idea might be to use so-called surrogate markers, indirect indicators that aging is slowed. Drug companies do that with other conditions, demonstrating, for example, that a drug lowers blood pressure or cholesterol levels, which are surrogates for reducing the risk of heart disease. But what is a surrogate marker for aging?
"You have to figure out: Are there parameters to aging other than the length of time you live?" says Dr. Ronald W. Hansen, an expert on the drug industry at the University of Rochester's Simon Graduate School of Business. Then, he adds, you need a way of measuring them.
But, Dr. Hansen cautions, proving a surrogate marker works "is going to take a very long time, particularly if this pill is something you need to take in your 30's and 40's."
Yet such markers must exist, researchers say. After all, said Dr. Douglas P. Kiel, director of medical research at the Hebrew Rehabilitation Center for the Aged in Boston and a professor at Harvard Medical School, people age at different rates.
Some scientists have proposed that more than two dozen blood chemicals, taken together, act as biological markers and might be linked to aging. These include measures of inflammation (one hypothesis says that inflammatory damage contributes to the physical signs of growing old). Levels of growth factor, a muscle-promoting, insulin-like substance that dips in concentration with age, may also be factors.
Other researchers prefer physical measurements. How fast do you walk? How quickly can you rise from a chair? How long can you stand on one foot with eyes closed?
Dr. Kiel and Dr. David Karasik, his colleague at the Hebrew Rehabilitation Center and a genetic epidemiologist at Harvard, are investigating another possible marker: the hand. They have developed a scorecard based on changes they can see in X-rays of things like bone spurs in the joints. They are studying hand X-rays taken in the 1960's from participants in the federal Framingham study, which follows residents of Framingham, Mass., and keeps records of their health. The hope is that those with lower hand-aging scores lived longer than others who were the same age but had higher scores.
Even an initial assessment of this hypothesis will take time. Dr. Karasik says he has read about 2,000 hand X-rays and has about 1,700 to go. He is cautious about his chances for success, noting that the National Institute on Aging has invested much time and money looking for a biological marker of aging, but nothing has panned out yet.
Moreover, it is not at all certain the Food and Drug Administration would accept any of the currently proposed surrogate markers for aging. In the meantime, the patent clocks on Elixir Pharmaceuticals and other companies' drugs will be ticking.
Dr. Guarente has a different strategy, he said,
based on the assumption that an anti-aging drug should protect against diseases that occur with age, like cancer, heart disease and diabetes. So, find a disease any disease Dr. Guarente said, and show that the putative anti-aging drug works against it. Then get the drug on the market as a treatment specific for that illness. The F.D.A. forbids companies from advertising or promoting drugs for any but approved uses. But doctors can prescribe drugs for other uses at their own discretion. And researchers could publish studies giving strong hints that the drug is, if not a fountain of youth, then a first step.
Dr. Guarente admits that he would have little choice but to use this roundabout strategy. "I don't see how else we could get something like that to market," he said.
