Newly developed antisense oligonucleotides (ASOs) that target superoxide dismutase 1 (SOD1) mRNA increase survival and improve muscle function in animal models of amyotrophic lateral sclerosis (ALS), a new study has shown. SOD1 mutation accounts for ~20% of familial ALS. In previous studies, an ASO against SOD1 was identified and tested, but interest in its development waned because its effects were modest and new advances promised more potent ASOs. In the new study, next-generation ASOs were identified by screening >2,000 ASOs against human SOD1. When these ASOs were injected into the cerebrospinal fluid of rats and mice that expressed mutant human SOD1, levels of human SOD1 mRNA were reduced, disease onset was delayed and survival was prolonged by 22% in mice and up to 39% in rats. Furthermore, ASO injection improved compound muscle action potentials, indicating a reversal of disease progression. A clinical trial of the ASOs in humans with SOD1-mediated ALS is now ongoing.