However, a recent study (van den Berg et al., 2024) reported that BIIBo78, an ASO for C9orf72-associated ALS in phase 1 trial, showed no ability to reduce neurofilament levels and no benefit to clinical outcomes relative to the placebo cohort, which has revealed the limitations of the gene-silencing method and the necessity of exploring multi-mechanism combination therapies. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.