Although C9ORF72 DPRs consistently demonstrate detrimental effects across several model systems [10], two early-stage randomized clinical trials (NCT03626012, NCT04931862) in C9-ALS patients have recently determined that antisense oligonucleotides (ASOs) targeting the sense-encoded repeat-containing transcript were not beneficial, and might even have adverse consequences [50]. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.