SOD1 and amyotrophic lateral sclerosis: The proof-of-principle of SOD1 gene silencing in mice with virally delivered shRNA has already been established192,193; more recently it was shown that subpial delivery of adeno-associated adenovirus serotype 9 prevented disease onset when injected before ALS onset, and blocked disease progression when delivered after onset.194 One promising therapeutic approach is gene modulation by antisense oligonucleotides (ASOs).