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Archive for Tuesday, September 7, 2004

Buildup of gunk targeted in Alzheimer’s research

September 7, 2004

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— How to prevent a sticky gunk from clogging up, and probably killing, the brain cells of Alzheimer's patients is the newest focus in the fight against the disease.

A half-dozen companies are developing drugs to target the buildup, and researchers are enrolling hundreds of patients to test the lead candidate -- although nobody yet knows if this gunk, called beta-amyloid, is the disease's true culprit.

But it's the chief suspect, and tests of these drugs could finally end a long-standing debate about the cause of Alzheimer's devastating symptoms.

"We have placed our bet on the amyloid hypothesis," is the way Dr. Eric Siemers of Eli Lilly & Co. puts it -- a statement that describes much of industry's focus.

The theory is that reducing this brain plaque will finally offer a way to do more than treat just the symptoms of Alzheimer's disease, as today's drugs do. But lest families' hopes get too high, even proponents expect anti-amyloid therapy is most likely to help mild disease, before too many neurons have died.

"If you're trying to control the disease process, you certainly want to treat people as early as possible," said Dr. Paul Aisen, a Georgetown University neurologist who is heading the largest U.S. study yet of an anti-amyloid drug, Neurochem Inc.'s Alzhemed.

About 4.5 million Americans have Alzheimer's, a creeping brain degeneration that slowly robs its victims of memory and the ability to reason, communicate and care for themselves. With the aging population, a staggering 14 million may have it by 2050.

No one knows what causes Alzheimer's. Some scientists think fibrous tangles of a protein called tau that builds up inside brain cells kills them.

But the leading theory is that something spurs abnormal production of another protein, beta-amyloid, which forms clumps that coat the outside of brain cells and kills them -- plaque that is the disease's trademark.

Different attempts to attack that plaque:

l Beta-amyloid initially floats in the blood and spinal fluid, until the sticky substance bonds with helper molecules to form chains that build into plaque. Alzhemed essentially coats beta-amyloid, reducing the stickiness so those chains can't form.

A Phase III study is enrolling about 500 patients around the country and in Canada to try to prove Alzhemed's effects.

l Lilly hopes to halt beta-amyloid formation in the first place. Its drug candidate blocks an enzyme called gamma secretase. The enzyme helps create beta-amyloid by clipping pieces that form it off a larger protein. In early studies, Alzheimer's patients given the still-unnamed drug for six weeks had a 40 percent reduction of beta-amyloid in their blood.

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