PMID- 19283860
OWN - NLM
STAT- MEDLINE
DCOM- 20090617
LR  - 20151119
IS  - 1542-9741 (Electronic)
IS  - 1542-9733 (Linking)
VI  - 86
IP  - 2
DP  - 2009 Apr
TI  - Postnatal development in cynomolgus monkeys following prenatal exposure to 
      natalizumab, an alpha4 integrin inhibitor.
PG  - 144-56
LID - 10.1002/bdrb.20193 [doi]
AB  - BACKGROUND: Natalizumab is a humanized monoclonal IgG4 antibody to human alpha4 
      integrin that blocks the interaction of alpha4beta1 and alpha4beta7 integrins 
      with their ligands, including fibronectin, vascular cell adhesion molecule-1, and 
      mucosal addressin cellular adhesion molecule-1. Because alpha4 integrins and 
      their ligands are widely involved in mammalian development, lymphopoeisis, and 
      hematopoiesis, natalizumab may interfere with these processes. METHODS: The 
      effects of prenatal exposure to natalizumab on postnatal development were 
      assessed in cynomolgus monkeys at doses of 0 and 30 mg/kg administered 
      intravenously every other day from gestational day (GD) 20 to 70 or GD 20 to 
      term. Infants were delivered by natural birth and evaluated for general health, 
      survival, development, and immunological structure and function at 12 or 18 
      months. RESULTS: An increase in abortions was seen in the first cohort of 
      natalizumab-treated dams (39.3 vs. 7.1% in the controls) but not in the second 
      cohort (33.3, 37.5%). Infants in the term treatment group had elevated lymphocyte 
      ( approximately 150%) and nucleated red blood cell counts ( approximately 400%), 
      consistent with the pharmacological effect of natalizumab, and reductions in 
      platelet counts ( approximately 28%), which were reversible following clearance 
      of natalizumab. No anemia was observed. Infants in the term treatment group had 
      significantly increased spleen weights at 12 months but not at 18 months. All 
      other experimental observations in infants from natalizumab-treated dams were 
      comparable with those of controls. CONCLUSION: Natalizumab had no adverse effects 
      on the general health, survival, development, or immunological structure and 
      function of infants born to dams treated with natalizumab during pregnancy.
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 - Osterburg, Ingrid
AU  - Osterburg I
FAU - Fuchs, Antje
AU  - Fuchs A
FAU - Buse, Eberhard
AU  - Buse E
FAU - Clarke, Janet
AU  - Clarke J
LA  - eng
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  - Abortion, Veterinary/chemically induced
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  - Body Weight/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Embryonic Development/drug effects
MH  - Female
MH  - Fetus/drug effects
MH  - Hematopoiesis/*drug effects
MH  - Integrin alpha4/*immunology
MH  - Leukocytosis/chemically induced
MH  - Lymphocyte Activation/drug effects
MH  - Lymphocyte Subsets/drug effects
MH  - Macaca fascicularis/*growth & development
MH  - Male
MH  - Milk/chemistry
MH  - Natalizumab
MH  - Pregnancy
MH  - Pregnancy Complications, Hematologic/chemically induced
MH  - Pregnancy Outcome
MH  - *Prenatal Exposure Delayed Effects
MH  - Random Allocation
MH  - Splenomegaly/*chemically induced
EDAT- 2009/03/14 09:00
MHDA- 2009/06/18 09:00
CRDT- 2009/03/14 09:00
PHST- 2009/03/14 09:00 [entrez]
PHST- 2009/03/14 09:00 [pubmed]
PHST- 2009/06/18 09:00 [medline]
AID - 10.1002/bdrb.20193 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2009 Apr;86(2):144-56. doi: 
      10.1002/bdrb.20193.