PMID- 19294679
OWN - NLM
STAT- MEDLINE
DCOM- 20090617
LR  - 20151119
IS  - 1542-9741 (Electronic)
IS  - 1542-9733 (Linking)
VI  - 86
IP  - 2
DP  - 2009 Apr
TI  - Effects of natalizumab, an alpha4 integrin inhibitor, on the development of 
      Hartley guinea pigs.
PG  - 98-107
LID - 10.1002/bdrb.20189 [doi]
AB  - 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. CONCLUSION: No 
      fetotoxicity or teratogenic effects were attributable to natalizumab in these 
      studies.
CI  - (c) 2009 Wiley-Liss, Inc.
FAU - Wehner, Nancy G
AU  - Wehner NG
AD  - Elan Pharmaceuticals, Inc., South San Francisco, California 94080, USA. 
      nancy.wehner@elan.com
FAU - Shopp, George
AU  - Shopp G
FAU - Rocca, Meredith S
AU  - Rocca MS
FAU - Clarke, Janet
AU  - Clarke J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Birth Defects Res B Dev Reprod Toxicol
JT  - Birth defects research. Part B, Developmental and reproductive toxicology
JID - 101155115
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Natalizumab)
RN  - 143198-26-9 (Integrin alpha4)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/blood/immunology/pharmacology/*toxicity
MH  - Antibodies, Monoclonal/blood/immunology/pharmacology/*toxicity
MH  - Antibodies, Monoclonal, Humanized
MH  - Antibody Formation
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Embryonic Development/*drug effects
MH  - Female
MH  - Fetus/abnormalities/*drug effects
MH  - Guinea Pigs/*embryology
MH  - Integrin alpha4/*immunology
MH  - Natalizumab
MH  - Organogenesis/drug effects
MH  - Pregnancy
MH  - Random Allocation
EDAT- 2009/03/19 09:00
MHDA- 2009/06/18 09:00
CRDT- 2009/03/19 09:00
PHST- 2009/03/19 09:00 [entrez]
PHST- 2009/03/19 09:00 [pubmed]
PHST- 2009/06/18 09:00 [medline]
AID - 10.1002/bdrb.20189 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2009 Apr;86(2):98-107. doi: 
      10.1002/bdrb.20189.