Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: Treatment experience in clinical practice

In amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1-ALS), the antisense oligonucleotide tofersen had been investigated in a phase III study (VALOR) and subsequently introduced in an expanded access program. In this study we assess neurofilament light chain (NfL) before and during tofersen treatment.In six SOD1-ALS patients treated with tofersen at three specialized ALS centers in Germany, NfL in cerebrospinal fluid (CSF-NfL) and/or serum (sNfL) were investigated using the ALS Functional Rating Scale Revised (ALSFRS-R) and ALS progression rate (ALS-PR), defined by monthly decline of ALSFRS-R.Three of the six SOD1-ALS patients reported a negative family history. Three patients harbored a homozygous c.272A > C, p.(Asp91Ala) mutation. These and two other patients showed slower progressing ALS (defined by ALS-PR