SOD1 and amyotrophic lateral sclerosis: Since ALS is an etiologically, genetically, and phenotypically heterogeneous syndrome,11,12 we elected to focus exclusively on patients with ALS with a subset of SOD1 mutations that result in unstable SOD1 proteins13 and are associated with a uniformly rapid rate of disease progression.14 We were cognizant that rapid disease progression would yield both advantages (e.g., large degree of measurable functional decline) and disadvantages (e.g., a highly aggressive form of disease might be most impervious to therapeutic efforts).