Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis. (January 2014)

• Record Type: Journal Article
• Authors: Axelsson, Markus; Malmeström, Clas; Gunnarsson, Martin; Zetterberg, Henrik; Sundström, Peter; Lycke, Jan; Svenningsson, Anders
• Is Part Of: Multiple sclerosis. Volume 20:Number 1(2014)
• Page Start: 43
• Page End: 50
• Publication Date: 2014-01
• Subjects: Multiple sclerosis -- immunosuppressive therapy -- mitoxantrone -- rituximab -- biomarkers -- cerebrospinal fluid -- neurofilament light protein -- glial fibrillary acidic protein -- CXCL13 -- axonal damage; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458513490544
• Languages: English
• ISSNs: 1352-4585

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.