Enzyme in Alzheimer's Onset ID'd

An enzyme suspected of playing a key role in Alzheimer's has finally been identified by scientists, an advance that could give drug companies a promising target for treating the mind-wasting disease.

Thursday, June 8th 2000, 12:00 am

By: News On 6

An enzyme suspected of playing a key role in Alzheimer's has finally been identified by scientists, an advance that could give drug companies a promising target for treating the mind-wasting disease.

The disease causes the development of deposits that are thought to kill brain cells. The deposits are created when a long, string-like protein is cut in two specific places.

Scientists believe a ``chemical scissors'' makes one of the cuts, calling it gamma secretase without ever actually identifying it.

But in today's issue of the journal Nature, scientists at Merck Research Laboratories in West Point, Pa., reported that they have found strong evidence that gamma secretase is actually presenilin 1.

Presenilin 1 has already been linked to a rare inherited form of Alzheimer's that strikes people in their 30s and 40s. The new work suggests it also plays a role in the more common, noninherited variety.

Working independently, a team at Harvard Medical School has also identified presenilin 1 as the enzyme. They will report their findings in the July issue of the journal Nature Cell Biology.

Dr. Dennis Selkoe, a neurobiologist on the Harvard team, said the finding still must be confirmed. But it provides drug companies a potential target to create drugs that block the action of the enzyme.

``This is not just pie-in-the-sky,'' Selkoe said. ``There is a palpable sense that knowing what gamma secretase is, we should be able to inhibit it.''

The report is the latest development in Alzheimer's research. Last year, scientists reported finding a vaccine that hinders development of brain deposits in mice and the discovery of beta-secretase, the enzyme that makes the other cut involved in the formation of deposits.

The cause of Alzheimer's is still not known, and effective drugs for humans are still a long way off, said Steve Gardell, director of biological chemistry for Merck.

``The significance of the work we described in our paper is it helps better define the target for possible therapeutic agents in Alzheimer's disease,'' he said. ``We are in the early stages of this drug development campaign.''

Sangram Sisodia, chairman of neurobiology at the University of Chicago, said he is not convinced gamma secretase is presenilin 1.

``This last piece of information to be published provides stronger data,'' he said of the Merck research. But he argued that presenilin 1 might just be an accessory to gamma secretase.