Plasma Neurofilament Light Chain as a Potential Biomarker of Presymptomatic Spinal Muscular Atrophy

ABSTRACT Introduction/Aims While neurofilament light chain is a promising biomarker in spinal muscular atrophy (SMA), its dynamics in presymptomatic patients have not yet been determined. This study aimed to analyze the plasma neurofilament light chain (pNfL) as a treatment response biomarker in patients with presymptomatic spinal muscular atrophy (SMA) undergoing nusinersen treatment. Methods Eight 5q‐SMA patients with three SMN2 copies (four presymptomatic patients from newborn screening and four symptomatic patients) were prospectively enrolled from August 2022 to June 2023. All patients received nusinersen treatment and were followed up for 660 days. pNfL levels were measured at baseline and throughout the treatment, analyzing their temporal changes and correlation with motor function outcomes. Results At baseline, presymptomatic patients exhibited higher pNfL levels than symptomatic patients (388.74 ng/L vs. 113.60 ng/L). During the loading phase, pNfL levels decreased markedly in both groups, with greater reductions in presymptomatic patients (94.64% vs. 79.50%). All presymptomatic patients achieved age‐appropriate motor milestones. Decreased pNfL levels correlated moderately with motor function improvements, as measured by CHOP INTEND ( r = −0.548, p < 0.01) and HINE‐2 scores ( r = −0.635, p < 0.01). Discussion pNfL is a promising biomarker for monitoring treatment response in patients with presymptomatic SMA, highlighting the importance of early diagnosis and treatment through newborn screening.