NEW YORK Two papers by Columbia and Harvard researchers report for the first time that astrocytes (the most abundant non-neuronal cells in the central nervous system), which carry a mutated gene known to cause some cases of amyotrophic lateral sclerosis (ALS/Lou Gehrig's disease), induce motor neuron death. This indicates that astrocytes may contribute to ALS by releasing a toxic factor that damages neurons. These findings, posted online by Nature Neuroscience on April 15, suggest that developing an effective therapy for ALS would require overcoming the destructive effects of astrocytes and replacing the damaged motor neurons, possibly by transplanting motor neurons derived from embryonic stem cells.

In ALS, there is a progressive degeneration of motor neurons, leading to paralysis and eventual death. In single cell culture studies at Columbia University Medical Center, Serge Przedborski, M.D., Ph.D., co-director of the Center for Motor Neuron Biology and Disease, and his colleagues found that astrocytes expressing a mutated form of a gene, superoxide dismutase (SOD1), killed only the neurons that degenerate in ALS, not other types of neurons, and that this was due to a soluble toxic factor released by the astrocytes. If this toxic factor can be identified in future studies, this finding may offer novel strategies for ALS therapy.

"It was previously thought that astrocytes were merely spectators watching their neighboring motor neurons die," said Dr. Przedborski, who is the Page & William Black Professor of Neurology and professor of pathology and cell biology at Columbia's College of Physicians & Surgeons. "With these results, we have learned they are not just spectators, they are major players. The astrocytes and their cellular environment are specifically causing motor neuron death.

"If these cell culture findings are faithfully modeling the situation occurring in
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Contact: Elizabeth Streich
eas2125@columbia.edu
212-305-6535
Columbia University Medical Center
15-Apr-2007