This result strongly suggests that the SOD1 antisense-oligonucleotide tofersen is leading to a positive response of a biomarker for disease aggressiveness in patients with a SOD1D91A mutation, confirming its causal contribution in a monogenic sense (homozygous variant) and suggesting at least a role as a risk factor contributing to ALS pathogenesis (heterozygous state). The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.