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

Authors

  • J. Kuhle,

    Corresponding author
    1. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
    2. Department of Neurology, University Hospital Basel, Basel, Switzerland
    • J. Kuhle, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, UK

      Tel.: +44 2078828241

      Fax: +44 2078828257

      e-mail: j.kuhle@qmul.ac.uk

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  • C. Malmeström,

    1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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  • M. Axelsson,

    1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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  • K. Plattner,

    1. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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  • Ö. Yaldizli,

    1. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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  • T. Derfuss,

    1. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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  • G. Giovannoni,

    1. Department of Neurology, University Hospital Basel, Basel, Switzerland
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  • L. Kappos,

    1. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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  • J. Lycke

    1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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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.

Aims of the study

We compared the coherence between NfL and neurofilament heavy chain (NfHSMI35) 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. NfHSMI35 was measured by an electrochemiluminescence-based immunoassay. NfL levels were determined previously by the UmanDiagnostics NF-light® assay.

Results

NfHSMI35 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 NfHSMI35 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 NfHSMI35 (28.3 vs 26.9 pg/ml, P = 0.086).

Conclusions

We confirm previous findings, indicating reduced axonal damage under natalizumab treatment by measuring NfHSMI35, using an assay with independent methodology. In comparison with NfHSMI35, NfL changes were more pronounced and the treatment effect also included patients in remission. Our results suggest that NfL is superior over NfHSMI35 as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials.

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