Healthy neighbors rescue degenerating motor neurons

The life or death of motor neurons in patients afflicted with amyotrophic lateral sclerosis (ALS) may rest with a somewhat overlooked group of support cells that helps guide, nourish and remove toxins from neurons.

Howard Hughes Medical Institute researchers and their colleagues have discovered that non-neuronal cells, called astrocytes and glia, can protect neurons containing ALS-causing mutations from degeneration. Their studies also show that if non-neuronal cells harbor ALS mutations, then damage can occur in neighboring motor neurons that are otherwise healthy.

According to the researchers, their findings suggest that it may be possible to insert healthy astrocytes into ALS patients to reduce or prevent motor-neuron degeneration. Motor neurons control muscle action, and they are progressively weakened in ALS, leading to paralysis and death.

The collaborating teams of researchers, which included Howard Hughes Medical Institute investigator Lawrence Goldstein, published their findings in the October 3, 2003, issue of the journal Science. Goldstein, Don Cleveland and their colleagues at the University of California at San Diego, collaborated with researchers at McGill University Health Care Centre in Montreal, Harvard University, Massachusetts General Hospital and Boston University School of Medicine.

The researchers studied an inherited form of ALS, in which the mutant gene SOD1 produces an aberrant form of the enzyme superoxide dismutase 1. The abnormal SOD1 enzyme plays a central role in the progression of the disease. Inherited forms of ALS constitute about ten percent of ALS cases, and mutations in SOD1 are responsible for about 20 percent of the inherited cases of ALS.

Although hereditary forms of ALS account for only a small fraction of the overall incidence of the disease, said Goldstein, they can nevertheless provide clues to

Contact: Jim Keeley
Howard Hughes Medical Institute

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