Abstract
Few diseases are as debilitating and inevitably lethal as amyotrophic lateral sclerosis (ALS). The disease typically strikes adults in midlife, causing paralysis and death within five years. The cause of most cases remains unknown, and the disease is untreatable. About 10 percent of patients have an inherited form of the disease. In 1993 a multicenter study reported that some cases of familial ALS arise because of mutations in the gene encoding the cytosolic form of the enzyme copper-zinc superoxide dismutase (SOD1).1 This enzyme detoxifies the superoxide anion, a ubiquitous byproduct of aerobic metabolism. As a free radical (free to diffuse . . .