Taxol May Help in Fight Against Alzheimer's

Dec. 19, 1997

Story by Roger Martin, (785) 864-7239

Contacts:
Dann Hayes, (785) 864-8855, email [email protected]
N. Kathryn Clark, (785) 864-8857, email [email protected]

TAXOL MAY HELP IN FIGHT AGAINST ALZHEIMER'S

LAWRENCE -- Taxol, already proven effective in fighting ovarian and breast cancer, may someday also help in the battle against Alzheimer's disease.

In laboratory studies, two University of Kansas scientists have used taxol to slow the damage done to brain cells by the poisonous protein fibers that cause Alzheimer's.

"We haven't tried this in animals or in humans," stressed Mary L. Michaelis, professor of pharmacology and toxicology.

She and Gunda I. Georg, professor of medicinal chemistry, will describe their studies in a forthcoming issue of the Journal of Neurochemistry, published by the international Society of Neurochemistry.

In clinical studies across the country, scientists are investigating the possibility that vitamin E, estrogen and anti-inflammatory drugs may help slow brain-cell damage in people with Alzheimer's. But Michaelis' group was the first to test taxol for this property.

It was an unlikely candidate for the job, she said. Taxol had only been used to halt rapidly dividing cancer cells. In adults, brain cells never divide.

Michaelis said that the poisonous protein fibers that cause Alzheimer's are made of small fragments of a larger protein. The fragments of this protein are called amyloids. Individually, they are harmless. In clusters, they become toxic and kill brain cells.

The normal function of the protein that gives rise to these fragments still hasn't been pinned down, Michaelis said.

A couple of years back, she said, a research group at the University of Pennsylvania in Philadelphia had theorized that taxol may help slow the withering of the branching ends of nerve cells that is the hallmark of the disease.

But the group didn't test the theory, she said. So Michaelis, Georg and their graduate students did.

One part of their experiment involved harvesting the brain cells of experimental animals and exposing them to the poisonous protein fibers. Without taxol protection, the cells died in about 48 hours.

In another phase of the work, the scientists added taxol to the laboratory dishes in which the brain cells were kept. In most cases, the scientists added the taxol just before dumping in the poisonous fibers.

"We'd give taxol a chance to do its work on the brain cells," Michaelis said.

In other cases, taxol was added two hours after the poisonous fibers.

"In all cases, the taxol seemed to slow the degeneration of the branching ends of nerve cells," Michaelis said. "The cells still look good up to seven days after the introduction of amyloids."

The work is far from being applied to human subjects. She said, "We don't know how this would translate into the brain and influence the actual disease process."

Michaelis said that she and her group were conducting experiments to understand the precise mechanism by which taxol protects brain cells.

Even if taxol someday proves to help people with Alzheimer's, it would only slow the disease, not halt it.

"We can't do that until we know why the protein fibers are getting there in the first place," she said.

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