NEFL and amyotrophic lateral sclerosis: This confluence of factors has facilitated the launch of the first-ever ALS prevention trial (NCT04856982) of a genetic therapy, tofersen, in carriers of highly penetrant SOD1 mutations, which are associated with rapidly progressive ALS.10 In this study, NfL levels are monitored monthly, and eligible presymptomatic people randomised to receive tofersen (an SOD1 antisense oligonucleotide) or placebo when NfL levels rise above a predefined threshold.