title: Neurofilament light and heavy subunits compared as therapeutic biomarkers in multiple sclerosis.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Kuhle
authors.forename: C
authors.initials: C
authors.lastname: Malmeström
authors.forename: M
authors.initials: M
authors.lastname: Axelsson
authors.forename: K
authors.initials: K
authors.lastname: Plattner
authors.forename: O
authors.initials: O
authors.lastname: Yaldizli
authors.forename: T
authors.initials: T
authors.lastname: Derfuss
authors.forename: G
authors.initials: G
authors.lastname: Giovannoni
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: J
authors.initials: J
authors.lastname: Lycke
mesh_terms: D000328:Adult; D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D000069442:Natalizumab; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D018709:Statistics, Nonparametric
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D000069442:Natalizumab; D016900:Neurofilament Proteins; C044882:neurofilament protein L; C051774:neurofilament protein H
keywords: cerebrospinal fluid; multiple sclerosis; natalizumab; neurofilament heavy chain; neurofilament light chain