The Dynamics of Neurofilament Light Chain in Spinal Muscular Atrophy

Area of Science:

• Neurology
• Biomarkers
• Genetics

Background:

• Newborn screening (NBS) for spinal muscular atrophy (SMA) enables early diagnosis and treatment.
• There's a need for fluid biomarkers to monitor disease activity and outcomes in neonates with SMA, especially those with delayed treatment access.

Purpose of the Study:

• To evaluate neurofilament light chain (NfL) levels as a biomarker for disease activity and outcomes in newborns and children with SMA.
• To correlate NfL levels with clinical, neurophysiological, and genetic variables.

Main Methods:

• Cross-sectional correlation of pretreatment serum and cerebrospinal fluid NfL levels with clinical and genetic factors in 45 individuals with SMA.
• Longitudinal evaluation of NfL levels in untreated individuals and those receiving nusinersen monotherapy.

Main Results:

• Significantly higher pretreatment serum NfL (sNfL) levels were observed in neonates with 2 SMN2 copies compared to those with ≥3 copies.
• sNfL levels correlated with postnatal age in neonates with 2 SMN2 copies.
• A combined model of sNfL, CMAP, and CHOP-INTEND better predicted motor outcomes in neonates at 2 years.
• Pretreatment sNfL increased in infants with ≥3 SMN2 copies who delayed treatment, despite stable motor function.

Conclusions:

• Children with 2 SMN2 copies exhibit active denervation during the neonatal period.
• sNfL provides early insights into SMA pathophysiology before clinical symptoms manifest.
• sNfL may help expedite treatment initiation for infants with SMA.