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J Cell Mol Med. 2020 Feb 7. doi: 10.1111/jcmm.14939. [Epub ahead of print]

Nusinersen treatment and cerebrospinal fluid neurofilaments: An explorative study on Spinal Muscular Atrophy type 3 patients.

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Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy.
Neurological Clinics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Physiopathology and Transplantation, Milan University and Neuro ICU, Milan, Italy.
Pediatric Intensive Care Unit, Mother & Child Anaesthesia and Emergency Departement, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Scientific institute IRCCS E Medea, Lecco, Italy.
Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.


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.


Nusinersen; neurofilaments; pharmacodynamics biomarker; spinal muscular atrophy

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