Preliminary insights into RNA in CSF of SMA patients after Nusinersen “loading dose”

Antisense oligonucleotide (ASO) nusinersen (Spinraza®) modulates the pre–mRNA splicing of the SMN2 gene, allowing rebalance of biologically active SMN. It is administered intrathecally via lumbar puncture after removing an equal amount of cerebrospinal fluid (CSF). Its effect was proven beneficial and approved since 2017 for SMA treatment. Since the direct effect of nusinersen on RNA metabolism, the aim of this project was to evaluate cell-free RNA (cfRNA) in CSF of SMA patients under ASOs treatment for biomarker discovery. Overall design: By RNA-sequencing approach, RNA obtained from CSF of SMA type 2 and 3 patients was processed after 6 months of nusinersen treatment, at fifth intrathecal injection (T6) and compared to baseline (T0).