PMID- 19278014
OWN - NLM
STAT- MEDLINE
DCOM- 20090617
LR  - 20151119
IS  - 1542-9741 (Electronic)
IS  - 1542-9733 (Linking)
VI  - 86
IP  - 2
DP  - 2009 Apr
TI  - Embryo/fetal development in cynomolgus monkeys exposed to natalizumab, an alpha4 
      integrin inhibitor.
PG  - 117-30
LID - 10.1002/bdrb.20190 [doi]
AB  - BACKGROUND: Natalizumab is a humanized monoclonal immunoglobulin G4 antibody to 
      human alpha4 integrin that binds to the alpha4 subunit of alpha4beta1 and 
      alpha4beta7 integrins, where it blocks the interaction of these integrins with 
      their ligands, including fibronectin, vascular cell adhesion molecule-1, and 
      mucosal addressin cellular adhesion molecule-1. Because alpha4 integrins and 
      their ligands appear to be involved in mammalian fetal development, it is 
      possible that natalizumab may interfere with these processes. METHODS: The 
      effects of natalizumab on fetal development were assessed in cynomolgus monkeys 
      at doses of 0, 3, 10, and 30 mg/kg administered intravenously every other day 
      from gestational day (GD) 20 to 70. Pregnancies were terminated by Cesarean 
      section at GD 100. RESULTS: Natalizumab treatment was not associated with 
      increased abortions. All fetuses were alive. No external, visceral, or skeletal 
      abnormalities were seen that were considered to be related to treatment with 
      natalizumab. No histopathological findings were seen in the heart, a target organ 
      of developmental toxicity with a small molecule inhibitor of alpha4 integrin. At 
      dose levels > or = 10 mg/kg, hematological and/or lymphoid effects were observed 
      in some fetuses, consisting of slight thymic atropy, increased extramedullary 
      hematopoiesis in the spleen with a corresponding decrease in the liver, increases 
      in WBC and nucleated RBC, decreases in RBC parameters, and decreases in lymphoid 
      CD20 staining. CONCLUSION: Natalizumab had no abortifacient or teratogenic 
      effects, but was associated with changes in fetal hematopoiesis and leukocyte 
      trafficking.
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 - Oneda, Satoru
AU  - Oneda S
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  - Atrophy
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Embryonic Development/*drug effects
MH  - Female
MH  - Fetus/abnormalities/*drug effects
MH  - Hematopoiesis, Extramedullary/*drug effects
MH  - Integrin alpha4/*immunology
MH  - Lymphocyte Activation/drug effects
MH  - Lymphocyte Subsets/drug effects
MH  - Macaca fascicularis/*embryology
MH  - Natalizumab
MH  - Organogenesis/drug effects
MH  - Pregnancy
MH  - Random Allocation
MH  - Thymus Gland/drug effects/embryology/pathology
EDAT- 2009/03/12 09:00
MHDA- 2009/06/18 09:00
CRDT- 2009/03/12 09:00
PHST- 2009/03/12 09:00 [entrez]
PHST- 2009/03/12 09:00 [pubmed]
PHST- 2009/06/18 09:00 [medline]
AID - 10.1002/bdrb.20190 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2009 Apr;86(2):117-30. doi: 
      10.1002/bdrb.20190.