In both phase 1/2 and phase 3 of tofersen trials, an antisense oligonucleotide (ASO) targeting SOD1 messenger RNA (mRNA) transcripts in ALS associated with mutations in SOD1, there was a significant reduction of NfL levels in the CSF and plasma, but no improvement in clinical endpoints could be demonstrated [84,85]. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.