n research, Lou Gehrig's disease slowed in mice
ASHINGTON - Scientists have used a
chemical to delay the onset of Lou Gehrig's disease in mice and prolong their lives by
blocking an enzyme crucial for cell death. The research, done at Harvard Medical School,
also holds promise in battling other degenerative nerve disorders that afflict millions.
The findings are expected to boost efforts by drug companies to create so-called ''caspase inhibitors'' safe enough to test in people suffering from a variety of brain diseases.
The research provides ''a compelling argument ... for the value of caspase inhibitors,'' Mark Gurney of the Pharmacia Corp., which is pursuing the compounds, wrote in a review accompanying the research in the journal Science.
''The idea is very worthwhile, no question about it,'' added Dr. Flint Beal, a Cornell University neurologist, although he cautioned that human testing is not yet planned.
About 30,000 Americans have Lou Gehrig's disease, formally known as amyotrophic lateral sclerosis. 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 as paralysis leaves them unable to eat or breathe.
Caspases are enzymes that signal a damaged or worn out cell to die. 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 instead activated to kill them.
If doctors could block the action of the caspases, important nerve cells could be saved.
''That's one of the things I find most exciting,'' said Dr. Robert M. Friedlander of Harvard and Brigham and Women's Hospital, who conducted the new ALS research. ''A drug that's going to work for one of these diseases is likely going to work'' for several.
Friedlander tested mice that were 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. The 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 an additional 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.
Equally important, Friedlander stressed, was the discovery that caspases don't just abruptly kill off a damaged cell. Instead, their activity in one cell is essentially contagious, affecting the secretion of toxic substances that make neighboring neurons too sick to work properly.
So while ''it's not a cure,'' he said giving the caspase-inhibiting chemical to mice very early in the disease apparently protected some neurons that caspases had just began to make sick.
Would it work in people? Nobody knows, but Friedlander did find in the spinal cords of ALS patients some activated caspase identical to that in sick mice.
Pharmaceutical companies are waiting for a better drug before testing it in humans, Friedlander said.
Half a dozen companies, including Pharmacia and Merck & Co. are trying to create caspase inhibitors. When asked if human tests were foreseeable within the year, Pharmacia's Gurney said not with his company's version; Merck officials did not comment.
This story ran on page A3 of the Boston Globe on 4/14/2000.
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