Serological Biomarker Profiles of Neurofilament Light Chain in Children and Adolescents with Spinal Muscular Atrophy and Healthy Controls

Background/Purpose: Biomarkers are critical for preclinical and clinical investigations of gene-specific therapies for monogenic neurodegenerative diseases such as spinal muscular atrophy (SMA). Digitized immunoassays enabled ultrasensitive measurements of CNS-derived proteins in blood. We evaluated the potential of serum neurofilament light chains (NfL) as biomarker in children and adolescents with SMA and determined age-/sex-specific reference values.

Methods: We measured NfL levels in serum (sNfL) and cerebral spinal fluid (cNfL) of 18 children with SMA and varying numbers of SMN2 copies receiving nusinersen by single-molecule array (SiMoA) assay and analyzed correlations with baseline characteristics and motor development. Additionally, we examined sNfL in 97 neurologically healthy children.

Results: Median sNfL levels in treatment-naive SMA patients with two SMN2 copies are higher than in those with >2 SMN2 copies (p < 0.001) as well as controls (p = 0.010) and decline during treatment. The median sNfL concentration of healthy controls is 4.73 pg/mL with no differences in sex (p = 0.486) but age (p < 0.001). In all children with SMA, sNfL levels correlate strongly with cNfL levels. In children with SMA and 2 SMN2 copies, sNfL values correlate with motor function, contrary to older SMA children with >2 SMN2 copies.

Conclusion: sNfL values of our pediatric control cohort may serve as reference/comparison source for future studies. Strong correlations between sNfL and cNfL together with motor function suggest sNfL as suitable blood biomarker for SMA disease activity in children with 2 SMN2 copies and those with >2 SMN2 copies within their initial stages during early childhood.

Publikationsverlauf

Artikel online veröffentlicht:
28. Oktober 2021