Enzyme discovery opens door0
to Alzheimer's-preventing drugs
1999 The New York Times
The long, brutal process that leads to Alzheimer's disease starts when a single enzyme snips a protein that protrudes from brain cells, leading to the release of toxic shards.
Now scientists, report that they have
found that enzyme, opening the door to developing drugs that might block it and if the drugs prove safe - prevent or slow the disease.
The discovery of the enzyme had eluded teams of scientists at universities and drug companies for more than a decade, though they had given it a name, betasecretase.
So many false claims of victory were announced that investigators automatically doubted anyone who claimed to have found it.
But experts say that the new work, by Dr. Martin Citron and his colleagues at Amgen, a biotechnology company in Thousand Oaks, Calif., is different - that it passes crucial tests of authenticity, convincing even some skeptics.
The report appears in today's issue of the journal Science.
Dr. Sangram Sisodia, chairman of the department of neurobiology, pharmacology and physiology at the University of Chicago, said that when he first heard of the Amgen result, he dismissed it.
"It's junk," he said at the time. "It has been junk after junk for 12 years." But he added, "When I read the paper, I was overwhelmed. The set of experiments in this paper was a tour de force."
His enthusiasm was shared by other scientists, also not connected with the study. "We now have a target, an identified
target for drug development," said Dr. Rudolph Tanzi, a professor of neurology at Harvard Medical School and, the Massachusetts General Hospital.
The hope, Citron said, is that such a drug might stop the progress of Alzheimer's disease in a person who has it, or even prevent it in those likely to develop it.
Still, Citron and other scientists emphasized that the development of a drug was still years away and that its success could not be predicted.
With the beta-secretase discovery, several scientists said, the field of Alzheimer's research is poised at the same place as AIDS research several years ago. That was when scientists discovered that the AIDS virus needed a protease - an enzyme that cuts protein - to replicate.
Drug companies seized on that discovery, searching for compounds to block the HIV protease.
Now protease inhibitors are on the market and are a vital part of AIDS therapy. Beta-secretase is also a protease, and its method of cutting, is similar to the method of the HIV protease.
"With beta-secretase, the field of Alzheimer's research has now been granted the same opportunity that AIDS researchers were granted," Tanzi said.
"This is as exciting for Alzheimer's research as the HIV protease enzyme was for AIDS research."
Dr. Norman Relkin, an Alzheimer's specialist at the Weill-Cornell Medical Center in New York, said there was no doubt about the potential unleashed by the discovery.
"This is one of the long-sought-after Holy Grails of Alzheimer's research," he said.