Introduction: Pathogenesis of spinal muscular atrophy (SMA) is not limited to motor neuron degeneration and many different cells and tissue types, especially glial cells and neuroinflammation, are thought to play a role in the process. We aimed to define the contribution of glial cell and neuroinflammation-related molecules to the SMA process and to identify biomarkers that may be diagnostic and/or predict the clinical response to nusinersen treatment.
Methods: Twenty-four adult SMA patients receiving nusinersen treatment and twelve healthy subjects were included. Four molecules associated with glial cells (GFAP and GDNF) and neuroinflammatory activity (YKL-40 and IL-6) were analyzed.
Results: SMA patients had higher cerebrospinal fluid (CSF) GFAP and IL-6 levels (p < 0.05) and lower GDNF levels (p < 0.05) compared to the controls. CSF levels of IL-6 and YKL-40 decreased and GDNF increased under nusinersen treatment (p < 0.05). Higher baseline CSF GFAP levels were associated with more favorable clinical responses to treatment.
Discussion: GFAP is a marker of both diagnostic and prognostic importance for SMA disease, and higher levels are associated with better clinical outcome. New therapies targeting glial cells and anti-inflammatory agents may have a positive impact on the clinical utility of current treatments.
Keywords: Astrocyte; Biomarker; GFAP; Neuroinflammation; Nusinersen.
© 2025. Fondazione Società Italiana di Neurologia.