CSF and plasma GFAP and VEGF in adult type 3 spinal muscular atrophy patients treated with nusinersen

INTRODUCTION: Nusinersen improves motor outcomes in SMA, but reliable biomarkers for treatment monitoring, especially in adults, are still lacking. We investigated cerebrospinal fluid (CSF) and plasma levels of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF), exploring their potential as biomarkers in disease progression. METHODS: This single-centre observational study included adults with type 3 SMA treated with nusinersen over 30 months. GFAP and VEGF levels in CSF and plasma were measured using ELISA at baseline, 14 and 30 months. Functional evaluation included Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and respiratory tests. Longitudinal data were evaluated using generalized linear mixed-effects models. A significance level of α = 0.05 was used in all analyses. RESULTS: Eleven patients were included (63.6% male, aged 19-60 at baseline). Improvements were observed in motor function, with an estimated non-linear increase of 9.02% (CI95%: 5.13-8.79) for RULM and an estimated average increase of 6.96 points (CI95%: 5.44-8.48) for HFMSE over 30 months of treatment. However, both CSF and plasma GFAP and VEGF levels changes at 14 and 30 months did not reach statistical significance, respectively (all p > 0.05). CONCLUSION: CSF and plasma GFAP and VEGF trajectories over a 30-month period under nusinersen treatment were nonsignificant. This study confirms sustained motor function improvements in adult type 3 SMA patients treated with nusinersen. Future research in larger, multicentric, and internationally collaborative cohorts are essential to fully understand the role of these potential biomarkers in SMA pathogenesis.