Nobel Prize-winner finds new path for Alzheimer's drug

After 25 years of ongoing research, Nobel Prize-winning scientist Paul Greengard is unveiling a new pathway at work in Alzheimer's--a discovery likely to trigger a fresh burst of R&D work around a new therapy for the mystery disease.

Alzheimer's has proved a vexing target for drug developers. Eli Lilly was bitterly disappointed to learn that its drug candidate actually appeared to make the disease worse in trial participants. And Medivation's Dimebon was scuttled by a failed late-stage study.

As the New York Times explains in its feature on Greengard's work, Lilly's scientists had focused on shutting down gamma secretase, which is needed to make beta amyloid, a common marker for the disease. But gamma secretase does more than generate the brain plaque, and drug developers who block it entirely may well hurt patients.

Greengard, though, found a protein that is needed by gamma secretase to produce beta amyloid--and only beta amyloid. A variation of Gleevec that can remain in the brain--something the current formulation can't accomplish--may be just what's needed.

"You could use Gleevec as a starting molecule," Harvard Alzheimer's expert Rudolph Tanzi tells the Times. "You could change the structure a little bit and try analogs until you get one that does what Gleevec does and does not get kicked out of the brain. That's possible."

- read the NYT story

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