Neurofilament light and heavy subunits compared as therapeutic biomarkers in multiple sclerosis

Acta Neurol Scand. 2013 Dec;128(6):e33-6. doi: 10.1111/ane.12151. Epub 2013 Jun 13.


Background: Neurofilaments are promising biomarkers in multiple sclerosis (MS) and increased levels in cerebrospinal fluid (CSF) indicate axonal damage or degeneration. In a previous study, neurofilament light chain (NfL) levels in CSF of relapsing remitting (RR) patients with MS were normalized by natalizumab treatment.

Aims of the study: We compared the coherence between NfL and neurofilament heavy chain (NfH(SMI) (35) ) levels in longitudinal CSF samples in a subset of these patients.

Methods: In 30 patients with RRMS, CSF was obtained prior to and following 12 months of natalizumab treatment. NfH(SMI) (35) was measured by an electrochemiluminescence-based immunoassay. NfL levels were determined previously by the UmanDiagnostics NF-light(®) assay.

Results: NfH(SMI) (35) decreased in 73.3% and NfL in 90% of the patients following natalizumab treatment (32.4 vs 27.4 pg/ml, P = 0.002 and 820 vs 375 pg/ml, P < 0.0001). Patients experiencing a relapse showed higher NfH(SMI) (35) levels compared with patients in remission (47.7 vs 27.6 pg/ml, n = 8, P = 0.001). This difference was less obvious for NfL (1055 vs 725 pg/ml, P = 0.256). In patients in remission, NfL levels were lower following natalizumab treatment (830 vs 365 pg/ml, n = 20, P = 0.0002), whereas the same comparison failed significance for NfH(SMI) (35) (28.3 vs 26.9 pg/ml, P = 0.086).

Conclusions: We confirm previous findings, indicating reduced axonal damage under natalizumab treatment by measuring NfH(SMI) (35) , using an assay with independent methodology. In comparison with NfH(SMI) (35) , NfL changes were more pronounced and the treatment effect also included patients in remission. Our results suggest that NfL is superior over NfH(SMI) (35) as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials.

Keywords: cerebrospinal fluid; multiple sclerosis; natalizumab; neurofilament heavy chain; neurofilament light chain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers / cerebrospinal fluid
  • Disability Evaluation
  • Female
  • Humans
  • Male
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / drug therapy
  • Natalizumab
  • Neurofilament Proteins / cerebrospinal fluid*
  • Statistics, Nonparametric


  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Natalizumab
  • Neurofilament Proteins
  • neurofilament protein L
  • neurofilament protein H