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Understanding the Noxious cause of Lou Gehrig's disease

September 14, 2007

There is no known cure for amyotrophic lateral sclerosis (ALS), often known as Lou Gehrig disease and motor neuron disease. ALS is a progressive, fatal, neurodegenerative disease caused by the degeneration of nerves that control voluntary muscle movement. New evidence generated in mice by John Engelhardt and colleagues at Iowa University, Iowa City, has provided insight into the mechanisms responsible for certain forms of the disease and has identified potential targets for the development of drugs to treat individuals with these forms of ALS.

In some individuals, ALS is caused by a mutation in their SOD1 gene. Mice overexpressing this mutant gene (SOD1G93A mice) develop ALS-like disease. In this study, the authors found that the rate of disease progression could be dramatically slowed and survival markedly improved if SOD1G93A mice lacked expression of either Nox1 or Nox2, although the effects were more dramatic in the absence of Nox2. The Nox1 and Nox2 genes are on the X-chromosome and female mice lacking just one copy of either gene showed delayed disease onset, indicating that even a 50% decrease in expression of these proteins provided some protection. These data have led to the suggestion that developing drugs to inhibit the Nox pathway might be of benefit to individuals with ALS.





Journal of Clinical Investigation



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