Unfortunately, most drugs have failed Phase 2 and 3 trials, which can be due to several reasons, including (1) poor human and mouse trial design; (2) the mutant SOD1 mouse model may not be predictive of the pathophysiological process in the more common sporadic form(s) of ALS; (3) lack of proper pharmacokinetics, (4) lack of pharmacodynamic markers in human studies; (5) lack of evidence for target engagement by candidate drugs in human studies. This evidence concerns the gene SOD1 and amyotrophic lateral sclerosis.