Neurofilament as a potential biomarker for spinal muscular atrophy

Basil T. Darras, Thomas O. Crawford, Richard S. Finkel, Eugenio Mercuri, Darryl C. De Vivo, Maryam Oskoui, Eduardo F. Tizzano, Monique M. Ryan, Francesco Muntoni, Guolin Zhao, John Staropoli, Alexander McCampbell, Marco Petrillo, Christopher Stebbins, Stephanie Fradette, Wildon Farwell, Charlotte J. Sumner

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Objective: To evaluate plasma phosphorylated neurofilament heavy chain (pNF-H) as a biomarker in spinal muscular atrophy (SMA). Methods: Levels of pNF-H were measured using the ProteinSimple® platform in plasma samples from infants with SMA enrolled in ENDEAR (NCT02193074) and infants/children without neurological disease. Results: Median pNF-H plasma level was 167.0 pg/mL (7.46–7,030; n = 34) in children without SMA (aged 7 weeks–18 years) and was higher in those aged < 1 versus 1–18 years (P = 0.0002). In ENDEAR participants with infantile-onset SMA, median baseline pNF-H level (15,400 pg/mL; 2390–50,100; n = 117) was ~10-fold higher than that of age-matched infants without SMA (P < 0.0001) and ~90-fold higher than children without SMA (P < 0.0001). Higher pretreatment pNF-H levels in infants with SMA were associated with younger age at symptom onset, diagnosis, and first dose; lower baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders score; and lower peroneal compound muscle potential amplitude. Nusinersen treatment was associated with a rapid and greater decline in pNF-H levels: nusinersen-treated infants experienced a steep 71.9% decline at 2 months to 90.1% decline at 10 months; sham control–treated infants declined steadily by 16.2% at 2 months and 60.3% at 10 months. Interpretation: Plasma pNF-H levels are elevated in infants with SMA. Levels inversely correlate with age at first dose and several markers of disease severity. Nusinersen treatment is associated with a significant decline in pNF-H levels followed by relative stabilization. Together these data suggest plasma pNF-H is a promising marker of disease activity/treatment response in infants with SMA.

Original languageEnglish (US)
Pages (from-to)932-944
Number of pages13
JournalAnnals of Clinical and Translational Neurology
Issue number5
StatePublished - May 2019

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology


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