title: Effects of natalizumab, an alpha4 integrin inhibitor, on the development of Hartley guinea pigs.
abstract: BACKGROUND
  Natalizumab is a humanized monoclonal immunoglobulin G4 antibody directed against the human alpha4 integrin subunit, disrupting interaction with its ligands. Natalizumab inhibits the interaction of alpha4 integrins with fibronectin, vascular cell adhesion molecule-1, and mucosal addressin cellular adhesion molecule-1, which are of potential importance in development. Two studies were undertaken to evaluate the effects of natalizumab on embryo/fetal development in guinea pigs.
  
  
  METHODS
  In the first study, pregnant guinea pigs were treated with intravenous injections of 3, 10, or 30 mg/kg natalizumab or vehicle every other day from gestational day (GD) 4 to 30. In the second study, females were treated on alternate days starting at least 28 days prior to mating through GD 30. Fetal examinations and histopathologic examination of the liver, heart, thymus, spleen, and intestinal tract were performed following maternal euthanasia on GD 59-62.
  
  
  RESULTS
  Natalizumab had no significant effect on embryo/fetal development in either study. Exposure to natalizumab during organogenesis did not result in treatment-related external, visceral, or skeletal variations or malformations or histopathologic changes.
  
  
  CONCLUSIONS
  No fetotoxicity or teratogenic effects were attributable to natalizumab in these studies.
authors.affiliation: Elan Pharmaceuticals, Inc., South San Francisco, California 94080, USA. nancy.wehner@elan.com
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Wehner
authors.forename: George
authors.initials: G
authors.lastname: Shopp
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Rocca
authors.forename: Janet
authors.initials: J
authors.lastname: Clarke
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000917:Antibody Formation; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000187:drug effects*; D006168:Guinea Pigs / Q000196:embryology*; D039441:Integrin alpha4 / Q000276:immunology*; D000069442:Natalizumab; D038081:Organogenesis / Q000187:drug effects; D011247:Pregnancy; D011897:Random Allocation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D039441:Integrin alpha4