The US Federal Drug Administration (FDA) approved sNfL levels as a surrogate marker for engagement of a relevant therapeutic target (SOD1) in SOD1-ALS.We hypothesized that a biomarker response to the SOD1-directed ASO tofersen could prove the causality of this mutation in both hetero- and homozygous SOD1D91A mutant patients. Here, SOD1 is linked to amyotrophic lateral sclerosis.