title: Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.
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.
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Axelsson
authors.forename: Clas
authors.initials: C
authors.lastname: Malmeström
authors.forename: Martin
authors.initials: M
authors.lastname: Gunnarsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Peter
authors.initials: P
authors.lastname: Sundström
authors.forename: Jan
authors.initials: J
authors.lastname: Lycke
authors.forename: Anders
authors.initials: A
authors.lastname: Svenningsson
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001369:Axons / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D000069283:Rituximab; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D000069283:Rituximab; D008942:Mitoxantrone
keywords: CXCL13; Multiple sclerosis; axonal damage; biomarkers; cerebrospinal fluid; glial fibrillary acidic protein; immunosuppressive therapy; mitoxantrone; neurofilament light protein; rituximab