C9orf72 and amyotrophic lateral sclerosis: However, several highly anticipated ASO drugs, namely one targeting Htt in Huntington disease (Tominersen) and two targeting the C9ORF72 sense repeat-containing transcript in C9ORF72-ALS/FTD (IONIS-C9Rx/BIIB078 and Wave WVE-004), all failed in clinical trials (Kingwell, 2021; Kwon, 2021; van den Berg et al, 2024), despite success in preclinical studies with mouse models (Jiang et al, 2016; Kordasiewicz et al, 2012; Liu et al, 2022; Tran et al, 2022).