Open AccessNusinersen treatment and cerebrospinal fluid neurofilaments: An explorative study on Spinal Muscular Atrophy type 3 patients
Author(s) -
Faravelli Irene,
Meneri Megi,
Saccomanno Domenica,
Velardo Daniele,
Abati Elena,
Gagliardi Delia,
Parente Valeria,
Petrozzi Lucia,
Ronchi Dario,
Stocchetti Nino,
Calderini Edoardo,
D’Angelo Grazia,
Chidini Giovanna,
Prandi Edi,
Ricci Giulia,
Siciliano Gabriele,
Bresolin Nereo,
Comi Giacomo Pietro,
Corti Stefania,
Magri Francesca,
Govoni Alessandra
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14939
Subject(s) - neurofilament , sma* , spinal muscular atrophy , cerebrospinal fluid , medicine , atrophy , biomarker , pathology , disease , biology , immunohistochemistry , biochemistry , mathematics , combinatorics
The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme‐linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response.