The rapid paralysis that killed baseball legend Lou Gehrig begins when neurons in the brain and spinal cord die mysteriously. Now, experiments with mice suggest a possible new treatment :. Drugs that push cell suicide
Amyotrophic lateral sclerosis (ALS), as Lou Gehrig's disease is formally known, crippled adults in their 40s and 50s and brings death within 1-5 years. The only treatment available just slightly increases the chances of survival, but it only works in the early phase of the disease. No other drugs were developed, because researchers were simply some clues about what went wrong. A breakthrough came in 1993, when they discovered that a gene called SOD1 was mutated in many ALS patients. Just how the mutation leads to disease is still unclear, but studies of human patients and transgenic mice with the defective gene have suggested that the mutation activates two enzymes called caspase-1 and -3. Caspases are beginning a process called programmed cell death, or apoptosis, which normally allows the orderly removal of aging, inefficient, or cancer cells. increased caspase activity in ALS has been suggested that apoptosis is unleashed, killing healthy and vital neurons.
To find out, use neurosurgeon Robert Friedlander and colleagues from Brigham and Women's Hospital in Boston, Columbia University, and the University of Chicago first several staining techniques to confirm that caspase was actually activated in mice with SOD1 mutation. Then, they used small pumps to inject a thread of a caspase inhibitor called zVAD-fmk directly into the brains of the mutated mice, while another group received infusion of a solution without the inhibitor.
The experiment was started when the mice were 60 days; from there, the animals receiving the caspase inhibitor took about 63 days to develop symptoms of ALS 20 days longer than the control group. They also lived 27 days more, reports the team in April 14 Science . Microscopic examination of their spinal cords showed the treated mice had more motor neurons left than controls. "We have not found a cure," warns Friedlander, but he is optimistic that the caspases can be a good lead for new drugs.
"The study offers an interesting new approach to treatment," agrees pharmacologist Mark Gurney Pharmacia Corp. in Kalamazoo, Mich. "It's an important step," adds -. ". But not a home run "
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