Neurofilaments as Biomarkers of Disease Activity and Treatment Response in Spinal Muscular Atrophy

Background: Neurofilament light chain (NfL) has been increasingly used in spinal muscular atrophy (SMA) to monitor disease progression and treatment response. Aims: We assessed plasma NfL before and after treatment with all three available therapies and in relation to SMA type, age, and functional level. Methods: We included all consecutive individuals with SMA who initiated treatment or switched from one treatment to another in whom plasma samples were available at baseline and 12 months post-treatment. Results: Our study included 73 individuals, with Type I (n = 13), II (n = 19), III (n = 33), IV SMA (n = 1) or individuals diagnosed before clinical onset (n = 7); 52/73 were treatment naïve and 21 were included at the time of switching to a new treatment. Mean age at baseline was 17 years, ranging from 0 to 47. At baseline, the NfL levels ranged from 4 to 2682 pg/mL. The overall 12-month changes ranged from -2582.3 to 112 pg/mL. A significant decrease in NfL over time (p < 0.001) was observed. Age was the strongest predictor of the magnitude of NfL reduction. The reduction was greatest in children < 2 years (83%), with progressively smaller reductions in older age groups. SMN2 copy number and SMA type had no significant interactions. Comparison among treatments was challenging because of cohorts' composition; in adults, risdiplam and nusinersen showed similar magnitudes of NfL changes. Conclusions: Our findings expand the literature on NfL in SMA, providing additional data of their changes in response to all three therapies and across a wide spectrum of age and severity.