Glial Fibrillary Acidic Protein in Cerebrospinal Fluid of Nusinersen-Treated Patients with Spinal Muscular Atrophy

Abstract BackgroundActivated astroglia is involved in the pathophysiology of neurodegenerative diseases and has also been described in animal models of spinal muscular atrophy (SMA). Given the urgent need of biomarkers for treatment monitoring of new RNA-modifying and gene replacement therapies in SMA, we examined glial fibrillary acidic protein (GFAP) concentrations as a marker of astrogliosis in the cerebrospinal fluid (CSF) of children and adult patients with SMA before and during treatment with nusinersen.Methods58 adult patients and 21 children with genetically confirmed 5q-associated SMA from 4 German motor neuron disease specialist care centers and 30 age- and sex-matched controls were prospectively included in this study. GFAP concentration was measured in CSF and motor performance and disease severity were assessed.ResultsCSF GFAP concentrations did not differ from controls but showed higher levels in more severely affected patients after adjustment for patients’ age. Within 14 months of nusinersen treatment, CSF GFAP concentrations did not change significantly.ConclusionsGFAP concentration in CSF of patients with long-standing SMA is not useful to assess disease severity or predict treatment response, but might support the hypothesis that glial activation is involved in SMA pathology.