SOD1 and amyotrophic lateral sclerosis: Early on, the role of reduced SOD1 activity in the pathogenesis of ALS was debated.18 However, the findings of normal enzymatic activity in patients with the p.D91A and six other mutations,12 the lack of correlation between SOD1 enzymatic activity and disease progression or age of onset,12 and the fact that SOD1 knockout mice do not develop ALS-like disease, contributed to the general view that reduced SOD1 activity does not cause ALS.