SOD1 and amyotrophic lateral sclerosis: Although overexpression of the transgene is an important limitation of these models, the significant correlation between the expression level of mutant SOD1 and the severity of MN degeneration (Alexander et al., 2004) paved the way for gene-silencing strategies using antisense oligonucleotides (ASOs) to treat mutant SOD1-mediated ALS (Smith et al., 2006; van Zundert and Brown, 2017).