title: Natalizumab in progressive MS: results of an open-label, phase 2A, proof-of-concept trial.
abstract: OBJECTIVE
  Natalizumab inhibits the migration of systemic immune cells to the CNS and may be beneficial in progressive multiple sclerosis (MS). The objective of the study was to examine the effects of natalizumab in progressive MS.
  
  
  METHODS
  In an open-label phase 2A study, 24 patients with progressive MS were included to receive natalizumab treatment for 60 weeks. Response to natalizumab was assessed in CSF and MRI studies. The primary endpoint was change in CSF osteopontin, a biomarker of intrathecal inflammation, from baseline to week 60.
  
  
  RESULTS
  Seventeen patients completed the study. No new safety issues were encountered. CSF osteopontin decreased by 65 ng/mL (95% confidence interval 34-96 ng/mL; p = 0.0004) from baseline to week 60 in conjunction with decreases in other CSF biomarkers of inflammation, axonal damage, and demyelination. Magnetization transfer ratio increased in both cortical gray and normal-appearing white matter and correlated with decreases in CSF neurofilament light chain.
  
  
  CONCLUSIONS
  Natalizumab treatment of progressive MS reduces intrathecal inflammation and tissue damage, supporting a beneficial effect of natalizumab treatment in progressive MS and suggesting that systemic inflammation contributes to the pathogenesis. Moreover, the study establishes the feasibility of using CSF biomarkers in proof-of-concept trials, allowing a low number of participants and short study duration.
  
  
  METHODS
  This study provides Class IV evidence that in patients with progressive MS, natalizumab reduces biomarkers of intrathecal inflammation.
authors.affiliation: From the Danish Multiple Sclerosis Center (J.R.C., R.R., L.B., P.S.S., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen; Danish Research Center for Magnetic Resonance (M.L., E.G., T.B.D., H.R.S.), Copenhagen University Hospital Hvidovre, Denmark.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Romme Christensen
authors.forename: Rikke
authors.initials: R
authors.lastname: Ratzer
authors.forename: Lars
authors.initials: L
authors.lastname: Börnsen
authors.forename: Mark
authors.initials: M
authors.lastname: Lyksborg
authors.forename: Ellen
authors.initials: E
authors.lastname: Garde
authors.forename: Tim B
authors.initials: TB
authors.lastname: Dyrby
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
authors.forename: Per S
authors.initials: PS
authors.lastname: Sorensen
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000473:pathology; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid; D004185:Disability Evaluation; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D004676:Myelin Basic Protein / Q000134:cerebrospinal fluid; D000069442:Natalizumab; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D053495:Osteopontin / Q000134:cerebrospinal fluid; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D007155:Immunologic Factors; C499048:MBP protein, human; D004676:Myelin Basic Protein; D000069442:Natalizumab; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D053495:Osteopontin; D020780:Matrix Metalloproteinase 9