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Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.

Journal article
Authors Markus Axelsson
Clas Malmeström
Martin Gunnarsson
Henrik Zetterberg
Peter Sundström
Jan Lycke
Anders Svenningsson
Published in Multiple sclerosis (Houndmills, Basingstoke, England)
Volume 20
Issue 1
Pages 43-50
ISSN 1477-0970
Publication year 2014
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 43-50
Language en
Links dx.doi.org/10.1177/1352458513490544
Keywords Multiple sclerosis, immunosuppressive therapy, mitoxantrone, rituximab, biomarkers, cerebrospinal fluid, neurofilament light protein, glial fibrillary acidic protein, CXCL13, axonal damage
Subject categories Basic Medicine, Neurochemistry

Abstract

BACKGROUND: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. OBJECTIVE: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). METHODS: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. RESULTS: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. CONCLUSIONS: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.

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Denna text är utskriven från följande webbsida:
http://www.gu.se/english/research/publication/?publicationId=184491
Utskriftsdatum: 2019-11-17