Chemical Prolongs Gehrig's Mice

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 effec ts. Pharmaceutical companies ''are waiting for a better drug,'' he said.

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