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Drug Shows Promise in Targeting Alzheimer's Root

NEW YORK - A preliminary study of an antibiotic drug showed promise in
reducing the plaque believed to be the root cause of Alzheimer's disease and
could lead to
the development of a new treatments, researchers reported on Monday.

A clinical trial of the drug, clioquinol, led by researchers at the University
of Melbourne in Australia, appeared to improve cognitive function in patients
with Alzheimer's by lowering levels of a protein known as beta-amyloid that is
thought
to be implicated in the build-up of plaque. Most Alzheimer's researchers
believe that the cause of the disease is formation of plaque in the brain.

But that has yet to be definitively proved. "The main importance of studies
like this
is to attempt to prove the principle that amyloid-lowering agents can stabilize
or possibly even reverse cognitive decline in Alzheimer's," said William Thies,
vice president of medical and scientific affairs at the Alzheimer's
Association. In a pilot trial of 36 patients with moderately severe Alzheimer's
disease who received the drug clioquinol, researchers found that beta-amyloid
levels declined in the clioquinol group and increased in the placebo group.
Patients taking clioquinol also performed better on a test of cognitive
ability.

The research, which appeared in the December issue of The Archives of
Neurology, suggests that clioquinol works by inhibiting zinc and copper ions
from binding to
beta-amyloid, helping to dissolve the protein and preventing it from
ac***ulating.

"The findings support a proof of concept in humans that a drug targeting
metal/beta-amyloid interactions can have a significant effect on beta-amyloid
metabolism, and through this, a beneficial modification on the progression of
Alzheimer's disease,"
the researchers said. Still, Thies said that while the trial is promising it is
too small to draw definitive conclusions. "The sample size is very, very small
and the effect is not dramatic." Now the researchers are applying to the U.S.
Food and Drug Administration to conduct a bigger trial, of 80 people.

But there are substantial safety concerns with clioquinol. The drug, introduced
more than 30 years ago as an antibiotic, was withdrawn after several thousand
people, mainly Japanese, developed vitamin B deficiencies that in some cases
led to blindness. The researchers said they are supplementing their patients
with
vitamin B and so far have seen no such symptoms.\

Even so, the company that holds the rights to the drug, Prana Biotechnology
Ltd.
of Australia, no longer plans to plow money into the drug. It will concentrate
on developing derivatives instead. Researchers plan to continue to study
clioquinol, however, in conjunction with
Sam Gandy, director of the Farber Institute for Neurosciences of Thomas
Jefferson University in Philadelphia.

"I think the general approach is extremely exciting," said Gandy. "At this
point in the field of Alzheimer's the most important question to answer is
whether plaque is causative of the disease or merely a bystander." Several
other companies, including Neurochem Inc., are developing drugs aimed at
inhibiting the development of amyloid protein or dissolving it once it is
formed.

There is some evidence that dissolving plaque reduces symptoms of the disease,
which range from memory loss to dementia. "Any study that establishes that an
anti-amyloid drug could stabilize or reverse cognitive decline would be a
landmark study," Gandy said.