Plasma Phosphorylated Neurofilament Heavy Chain (pNF-H) Level is Associated with Future Motor Function in Nusinersen-treated Individuals with Later-onset Spinal Muscular Atrophy (SMA)
Michelle A Farrar1, Francesco Muntoni2, Charlotte J Sumner3, Thomas O Crawford4, Richard S Finkel5, Eugenio Mercuri6, Xiaotong Jiang7, Jihee Sohn7, Marco Petrillo7, Steve Garafalo7, Wildon Farwell7
1Sydney Children’s Hospital and UNSW Sydney, 2UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital Foundation Trust, 3Departments of Neurology and Neuroscience, 4Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 5Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, 6Department of Paediatric Neurology, Catholic University Rome, 7Biogen
To evaluate the association between plasma phosphorylated neurofilament heavy chain (pNF-H) levels and clinical motor function endpoints in nusinersen-treated individuals with later-onset spinal muscular atrophy (SMA) who participated in the CHERISH/SHINE studies.

Neurofilament (NF) isoforms are major structural proteins of the neuronal cytoskeleton and are released into interstitial fluid following axonal damage or neuronal degeneration. Elevated NF levels have been detected in neurodegenerative disorders, including SMA.  


Individuals treated with nusinersen in the Phase 3, randomized, double-blind CHERISH study could transition to the open-label SHINE extension study (NCT02594124). Plasma pNF-H levels were measured using the pNF-H SimplePlex ELLA assay (ProteinSimple); motor function was assessed using the Hammersmith Functional Motor Scale – Expanded (HFMSE) and Revised Upper Limb Module (RULM). Linear multivariate regression models were applied to determine any relationship between log pNF-H levels at baseline and change from baseline in HFMSE or RULM to Day 450, 690, 930, 1170, or 1410.


pNF-H data were available for up to 75 participants with HFMSE/RULM data. After controlling for age at treatment initiation and baseline motor function, higher baseline log pNF-H level was not significantly associated with change in HFMSE or RULM at Days 450, 690 or 930. Higher baseline log pNF-H level was significantly associated with greater improvements in HFMSE and RULM at Days 1170 and 1410. The relationship between higher baseline pNF-H and improvement in HFMSE and RULM increased over time. Additional analyses will be presented.


These results show that participants with higher pNF-H levels at baseline are expected to have higher HFMSE and/or RULM scores relative to baseline at later visits after receiving nusinersen. pNF-H may be a useful indicator of future motor function and warrants further evaluation as a biomarker of treatment response in SMA.

Supported by: Biogen