Carlos Camara-Lemarroy1, Luanne Metz2, Jens Kuhle3, David Leppert3, Eline Willemse3, David Kb Li4, Anthony Traboulsee5, Jamie Greenfield6, Graziela Cerchiaro6, Claudia Silva2, V Wee Yong2. 1. Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada/Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada/School of Medicine, UANL, Monterrey, Mexico. 2. Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada/Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. 3. Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 4. Department of Medicine, The University of British Columbia, Vancouver, BC, Canada/Department of Radiology, The University of British Columbia, Vancouver, BC, Canada. 5. Department of Medicine, The University of British Columbia, Vancouver, BC, Canada. 6. Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Abstract
BACKGROUND: In the trial of Minocycline in Clinically Isolated Syndrome (MinoCIS), minocycline significantly reduced the risk of conversion to clinically definite multiple sclerosis (CDMS). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers in MS, and minocycline modulates matrix metalloproteinases (MMPs). OBJECTIVE: To assess the value of blood NfL and GFAP as a biomarker of baseline and future disease activity and its utility to monitor treatment response in minocycline-treated patients with clinically isolated syndrome (CIS). METHODS: We measured NfL, GFAP, and MMPs in blood samples from 96 patients with CIS from the MinoCIS study and compared biomarkers with clinical and radiologic characteristics and outcome. RESULTS: At baseline, NfL levels correlated with T2 lesion load and number of gadolinium-enhancing lesions. Baseline NfL levels predicted conversion into CDMS at month 6. GFAP levels at baseline were correlated with T2 lesion volume. Minocycline treatment significantly increased NfL levels at 3 months but not at 6 months, and decreased GFAP levels at month 6. Minocycline decreased MMP-7 concentrations at month 1. DISCUSSION: Blood NfL levels are associated with measures of disease activity in CIS and have prognostic value. Minocycline increased NfL levels at month 3, but reduced GFAP and MMP-7 levels.
BACKGROUND: In the trial of Minocycline in Clinically Isolated Syndrome (MinoCIS), minocycline significantly reduced the risk of conversion to clinically definite multiple sclerosis (CDMS). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers in MS, and minocycline modulates matrix metalloproteinases (MMPs). OBJECTIVE: To assess the value of blood NfL and GFAP as a biomarker of baseline and future disease activity and its utility to monitor treatment response in minocycline-treated patients with clinically isolated syndrome (CIS). METHODS: We measured NfL, GFAP, and MMPs in blood samples from 96 patients with CIS from the MinoCIS study and compared biomarkers with clinical and radiologic characteristics and outcome. RESULTS: At baseline, NfL levels correlated with T2 lesion load and number of gadolinium-enhancing lesions. Baseline NfL levels predicted conversion into CDMS at month 6. GFAP levels at baseline were correlated with T2 lesion volume. Minocycline treatment significantly increased NfL levels at 3 months but not at 6 months, and decreased GFAP levels at month 6. Minocycline decreased MMP-7 concentrations at month 1. DISCUSSION: Blood NfL levels are associated with measures of disease activity in CIS and have prognostic value. Minocycline increased NfL levels at month 3, but reduced GFAP and MMP-7 levels.
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