title: Intrathecal effects of daclizumab treatment of multiple sclerosis.
abstract: OBJECTIVE
  We previously reported that daclizumab, a humanized monoclonal antibody against CD25, reduced contrast-enhancing lesions (CEL) in patients with multiple sclerosis (MS) who were suboptimal responders to interferon-β and that this response correlated with expansion of CD56(bright) NK cells. These data have been reproduced in a placebo-controlled multicenter trial (CHOICE study). The current study investigates whether daclizumab monotherapy reduces CEL in untreated patients with relapsing-remitting MS (RRMS) and the effects of daclizumab on the intrathecal immune system.
  
  
  METHODS
  Sixteen patients with RRMS with high inflammatory activity were enrolled in an open-label, baseline-vs-treatment, phase II trial of daclizumab monotherapy for 54 weeks and followed by serial clinical and MRI examinations and immunologic biomarkers measured in the whole blood and CSF.
  
  
  RESULTS
  The trial achieved predefined outcomes. There was an 87.7% reduction in brain CEL (primary) and improvements in Multiple Sclerosis Functional Composite (secondary), Scripps Neurologic Rating Scale, and Expanded Disability Status Scale (tertiary) outcomes. There was significant expansion of CD56(bright) NK cells in peripheral blood and CSF, with resultant decrease in T cells/NK cells and B cells/NK cells ratios and IL-12p40 in the CSF. Surprisingly, CD25 Tac epitope was equally blocked on the immune cells in the CSF and in peripheral blood.
  
  
  CONCLUSIONS
  Daclizumab monotherapy inhibits formation of MS plaques in patients with RRMS and immunoregulatory NK cells may suppress activation of pathogenic immune responses directly in the CNS compartment.
  
  
  METHODS
  The study provides Class III evidence that daclizumab reduces the number of contrast-enhancing lesions in treatment-naive patients with RRMS over a 54-week period.
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Bibi.Bielekova@nih.gov
authors.forename: B
authors.initials: B
authors.lastname: Bielekova
authors.forename: N
authors.initials: N
authors.lastname: Richert
authors.forename: M L
authors.initials: ML
authors.lastname: Herman
authors.forename: J
authors.initials: J
authors.lastname: Ohayon
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: H
authors.initials: H
authors.lastname: McFarland
authors.forename: R
authors.initials: R
authors.lastname: Martin
authors.forename: G
authors.initials: G
authors.lastname: Blevins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D015703:Antigens, CD / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D000077561:Daclizumab; D004185:Disability Evaluation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007278:Injections, Spinal / Q000379:methods; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D009460:Neurologic Examination; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab
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