title: Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab.
abstract: OBJECTIVE
  The impact of present disease-modifying treatments (DMTs) in multiple sclerosis (MS) on nerve injury and reactive astrogliosis is still unclear. Therefore, we studied the effect of natalizumab treatment on the release of 2 brain-specific tissue damage markers into cerebrospinal fluid (CSF) in MS patients.
  
  
  METHODS
  CSF samples from 92 patients with relapsing forms of MS were collected in a prospective manner prior to natalizumab treatment and after 6 or 12 months. In 86 cases, natalizumab was used as second-line DMT due to breakthrough of disease activity. The levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were determined using highly sensitive in-house developed enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Natalizumab treatment led to a 3-fold reduction of NFL levels, from a mean value of 1,300 (standard deviation [SD], 2,200) to 400 (SD, 270) ng/l (p < 0.001). The later value was not significantly different from that found in healthy control subjects (350 ng/l; SD, 170; n = 28). Subgroup analysis revealed a consistent effect on NFL release, regardless of previous DMT or whether patients had relapses or were in remission within 3 months prior to natalizumab treatment. No differences between pre- and post-treatment levels of GFAP were detected.
  
  
  CONCLUSIONS
  Our data demonstrate that natalizumab treatment reduces the accumulation of nerve injury in relapsing forms of MS. It is anticipated that highly effective anti-inflammatory treatment can reduce axonal loss, thereby preventing development of permanent neurological disability.
authors.affiliation: Department of Neurology, Örebro University Hospital, Örebro, Göteborg.
authors.forename: Martin
authors.initials: M
authors.lastname: Gunnarsson
authors.forename: Clas
authors.initials: C
authors.lastname: Malmeström
authors.forename: Markus
authors.initials: M
authors.lastname: Axelsson
authors.forename: Peter
authors.initials: P
authors.lastname: Sundström
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dahle
authors.forename: Magnus
authors.initials: M
authors.lastname: Vrethem
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.forename: Niklas
authors.initials: N
authors.lastname: Norgren
authors.forename: Lars
authors.initials: L
authors.lastname: Rosengren
authors.forename: Anders
authors.initials: A
authors.lastname: Svenningsson
authors.forename: Jan
authors.initials: J
authors.lastname: Lycke
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001369:Axons / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid* / Q000187:drug effects; D005911:Gliosis / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D039441:Integrin alpha4 / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid* / Q000187:drug effects; D012008:Recurrence; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005904:Glial Fibrillary Acidic Protein; D000069442:Natalizumab; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D016875:tau Proteins; D039441:Integrin alpha4