{
  "abstract": "Introduction Advances in ultrasensitive assay techniques have enabled precise quantification of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP), highlighting their potential as dynamic biomarkers for detecting neuroaxonal injury, disease activity and progression in multiple sclerosis (MS). In the NeuroFilMS study, sNfL is being investigated prospectively as a prognostic biomarker for clinical and radiological disease activity in relapsing MS, while sGFAP is retrospectively explored as a marker of disease progression. The aim is to assess whether longitudinal monitoring of sNfL can inform diagnostic and therapeutic decisions in the treatment of people with MS (pwMS) and whether retrospective sGFAP measurements provide additional insights into disease progression. The study additionally aims to evaluate the comparability of different assay methods.Methods and analysis NeuroFilMS is a prospective, multicentre study that will be conducted across multiple MS study centres throughout Germany, in collaboration with the German Multiple Sclerosis Registry set up by the German National Multiple Sclerosis Society (Deutsche Multiple Sklerose Gesellschaft). The study aims to enrol 1500 pwMS diagnosed with relapsing MS. Participants will be randomised in a 2:1 ratio (n=1000 vs n=500) to either immediate sNfL reporting or delayed sNfL reporting to treating physicians, in order to evaluate how sNfL availability influences therapeutic decision-making in routine healthcare regarding diagnostics and therapy decisions. Over a 2-year follow-up period, pwMS will attend three study visits integrated into routine care, including blood sampling for sNfL, clinical evaluations and routine MRI assessments; sGFAP will be measured retrospectively in batches, as it is not currently available for routine diagnostic use. The study follows the standardised protocols for biosample collection, performed both within clinical routine laboratory procedures and through research collaboration. Statistical analyses will involve both descriptive and inferential methods to evaluate biomarker performance and clinical associations.Ethics and dissemination The study has received ethical approval from the Clinical Ethics Committee of Charité–Universitätsmedizin Berlin (EA4/136/24) and will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Findings will be disseminated through peer-reviewed publications, conference presentations and engagement with patient organisations and clinical networks.Trial registration number DRKS00034337.",
  "authors": [
    {
      "affiliations": [
        "Experimental and Clinical Research Center, Charité–Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany",
        "Institute of Medical Immunology, Charité–Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany",
        "Neuroscience Clinical Research Center, Charité–Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany"
      ],
      "name": "Rebekka Rust"
    },
    {
      "affiliations": [
        "Experimental and Clinical Research Center, Charité–Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany",
        "Neuroscience Clinical Research Center, Charité–Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany",
        "Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark",
        "The Center for Neurological Research, Department of Neurology, Slagelse Hospitals, Slagelse, Denmark"
      ],
      "name": "Sara Samadzadeh"
    },
    {
      "affiliations": [
        "German Multiple Sclerosis Registry, MS Research and Project Development Society, Berlin, Germany"
      ],
      "name": "Anna-Lena Röper"
    },
    {
      "affiliations": [
        "German Multiple Sclerosis Registry, MS Research and Project Development Society, Berlin, Germany"
      ],
      "name": "Alexander Stahmann"
    },
    {
      "affiliations": [
        "Experimental and Clinical Research Center, Charité–Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany",
        "Neuroscience Clinical Research Center, Charité–Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany"
      ],
      "name": "Patrick Schindler"
    },
    {
      "affiliations": [
        "Institute of Clinical Chemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"
      ],
      "name": "Michael Neumaier"
    },
    {
      "affiliations": [
        "Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"
      ],
      "name": "Hans-Werner Rausch"
    },
    {
      "affiliations": [
        "Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"
      ],
      "name": "Lucas Schirmer"
    },
    {
      "affiliations": [
        "Multiple Sclerosis Center and Research Center for Clinical Neuroimmunology and Neuroscience, Departments of Neurology, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland"
      ],
      "name": "Jens Kuhle"
    },
    {
      "affiliations": [
        "Department of Neurology, University Hospital Ulm, Ulm, Germany"
      ],
      "name": "Hayrettin Tumani"
    },
    {
      "affiliations": [
        "Experimental and Clinical Research Center, Charité–Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany",
        "Neuroscience Clinical Research Center, Charité–Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany"
      ],
      "name": "Friedemann Paul"
    },
    {
      "affiliations": [
        "Experimental and Clinical Research Center, Charité–Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany",
        "Neuroscience Clinical Research Center, Charité–Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany"
      ],
      "name": "Lina Samira Bahr"
    }
  ],
  "title": "Application of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) as biomarkers in the clinical management of multiple sclerosis (NeuroFilMS): a protocol for an observational cohort study",
  "uid": "6e2b5042-0d1d-5cdf-86c9-2bf2c9469ceb"
}