WESTPORT, Dec 30 (Reuters Health) - In an animal model of familial amyotrophic lateral sclerosis (ALS) generated by overexpression of mutant human copper zinc superoxide dismutase 1, copper chelators appear to increase survival of motor neurons.

In research conducted at the Universite Louis Pasteur de Strasbourg, France, Dr. Mimoun Azzouz, who is now affiliated with the Division of Surgical Research and Gene Therapy Center of Lausanne, Switzerland, and colleagues used transgenic ALS mice that overexpress superoxide dismutase 1 with a substitution of glycine to alanine at position 93. The mutation results in decreased neurite outgrowth and a decrease in motor neuron survival that is 46% less than in wild-type mice.

The investigators hypothesized that the superoxide dismutase 1 mutation may cause an alteration in the folding of SOD1, causing a release of copper and zinc. Copper toxicity may be the cause of motor neuron death.

Dr. Azzouz's team treated wild-type and mutant embryonic spinal motor neurons with copper chelators. They saw that viability was increased by more than 200% in the mutant motor neurons but that copper chelators had no effect on viability of wild-type neurons.

The investigators say, in the January issue of the Journal of Neurobiology, that the findings suggest that "...elimination of the toxic effect of copper is necessary to obtain full efficacy of neurotrophic factors in [familial amyotrophic lateral sclerosis] animals." The findings may have therapeutic implications in ALS, they add.

J Neurobiol 2000;42:49-55.