Chemical Prolongs Gehrig's Mice

.c The Associated Press

WASHINGTON (AP) - An experimental chemical significantly prolonged
the lives of mice with Lou Gehrig's disease by blocking an enzyme
crucial for cell death, a finding that holds promise not just for
this killer but for other nervous-system diseases that afflict
millions.

The research at Harvard Medical School may boost efforts already
under way by half a dozen drug companies to create ``caspase
inhibitors'' safe enough to test in people.

The new findings ``provide a compelling argument ... for the value of
caspase inhibitors,'' Mark Gurney of the Pharmacia Corp., one
drugmaker hunting such compounds, wrote in a review accompanying the
research in Friday's edition of the journal Science.

``The idea is very worthwhile, no question about it,'' added Cornell
University neurologist Dr. Flint Beal, although he cautioned that
human testing is not yet planned.

Some 30,000 Americans have Lou Gehrig's disease, formally known as
amyotrophic lateral sclerosis or ALS. No one knows the cause, but it
results in a creeping paralysis as neurons, or nerve cells, in the
brain and spinal cord that control movement are progressively
destroyed. On average, patients die within five years of the first
symptoms.

Caspases are enzymes that signal a damaged or worn-out cell to commit
suicide. Scientists now believe that in a variety of brain diseases -
from ALS and Alzheimer's to Parkinson's disease and strokes -
caspases that should be lying dormant inside fairly healthy neurons
are somehow activated to kill them instead.

So if doctors could block caspases' action, they might be able to
save important nerve cells.

Dr. Robert Friedlander of Harvard and Brigham and Women's Hospital
tested mice genetically engineered to get the human version of ALS.
He implanted miniature pumps in their brains to bathe neurons with an
experimental caspase-inhibiting chemical called zVAD-fmk.

Treated mice showed ALS symptoms 20 days later than untreated mice -
a long time in a mouse's lifespan - and they lived 22 percent longer,
he reports in Science.

If humans had a similar result, that would equal another 14 months of
life, said Dr. Leon Charash, medical adviser to the Muscular
Dystrophy Association, which helped fund Friedlander's work. In
contrast, the only ALS drug sold today prolongs survival by about
three months.

Would it work in people? Nobody knows, but Friedlander did find some
activated caspase in the spinal cords of ALS patients identical to
that in sick mice, a good sign.

He wants to test zVAD in people, but said manufacturer Enzyme Systems
Inc. fears the chemical - created solely for laboratory, not human,
use - could cause toxic side effects. Pharmaceutical companies ``are
waiting for a better drug,'' he said.

AP-NY-04-13-00 1400EDT