643 The dynamic of changes of pNFH levels in the CSF compared with the motor scales’ scores during three years of nusinersen treatment in children with spinal muscular atrophy types 2 and 3

Abstract

Neurofilaments are crucial in neuronal cytoskeleton formation, influencing axonal
growth and impulse modulation. This study focuses on understanding the dynamics of the phosphorylated neurofilament heavy subunit (pNFH) in pediatric spinal muscular atrophy (SMA) patients undergoing Nusinersen treatment. The presence of five neurofilament types, particularly
pNFH, is explored as a potential biomarker. SMA, an autosomal recessive disease impacting motor
neurons, is characterized by disease severity linked to the number of SMN2 gene copies. Approved
drugs, including Nusinersen, have demonstrated efficacy in enhancing motor activity. Methods: A
retrospective analysis was conducted on 18 pediatric SMA patients treated with Nusinersen from
October 2018 to July 2023. Cerebrospinal fluid (CSF) samples were utilized to assess pNFH levels.
Motor scales were employed to evaluate performance, focusing on patients with varying SMN2 gene
copies. Results: Following the initiation of Nusinersen treatment, a substantial decrease in pNFH
levels was observed in CSF samples. Motor scales indicated improved performance, particularly in
patients with more SMN2 copies. However, the correlation between pNFH levels and motor improvement was not strongly evident, suggesting a limited role as a prognostic indicator within this
timeframe. Conclusion: Nusinersen effectively reduced pNFH levels in pediatric SMA patients,
showcasing promising outcomes in motor function. However, the predictive value of pNFH remains inconclusive, emphasizing the need for further research. Study limitations, including the rarity of SMA, the absence of a control group, and the disease's dynamic nature over time, should be
considered when interpreting these findings.