March 2001

An End to Alzheimer's?

Isolation of key genes at the heart of Alzheimer's disease has set off a frenzied race to find a drug to stop this cruel affliction in its tracks.

By Ken Garber

When molecular biologist Bob Vassar joined biotech giant Amgen in 1996, his mother was suffering from advanced-stage Alzheimer's disease. For years he'd taken care of her himself, since his father had died young. "Once she became incontinent I couldn't keep her at home any more," he recalls with more than a trace of guilt. In a nursing home, Vassar's mother slid rapidly downhill. In 1999, at age 78, she died-17 years after her diagnosis of Alzheimer's, which gradually but inexorably drains its victims of memory, judgment and reason.

Vassar was helpless to stop, or even slow, his mother's descent into dementia. But unlike most Alzheimer's caregivers, he was in a position to help others avoid her fate. At Amgen, in Thousand Oaks, CA, he designed and implemented an ingenious method for isolating the gene for an enzyme called beta-secretase-a key culprit in the disease. "It was a high-risk project, and there was no guarantee we could get it," says Vassar. In fact, his group individually tested 860,000 gene copies before finding beta-secretase and publishing the discovery in late 1999.

With success came hope. The U.S. Food and Drug Administration has approved three drugs for Alzheimer's disease, but these only temporarily improve brain function, without slowing or stopping progression of the disease. Other treatments are in advanced development (see "Bulging Pipeline" sidebar), but none has yet shown good long-term results. The discovery of beta-secretase, on the other hand, opens the possibility of halting the disease. "It's a huge leap forward," says Lennart Mucke, director of the Gladstone Institute of Neurological Disease at the University of California, San Francisco. Possession of beta-secretase (discovered, almost simultaneously, by three other drug companies) has now set off a frenzied race to find and test a drug to block the enzyme and stop Alzheimer's in its tracks.