Critical period for a teratogenic VLA-4 antagonist: Developmental effects and comparison of embryo drug concentrations of teratogenic and non-teratogenic VLA-4 antagonists.

@article{Crofts2004CriticalPF,
  title={Critical period for a teratogenic VLA-4 antagonist: Developmental effects and comparison of embryo drug concentrations of teratogenic and non-teratogenic VLA-4 antagonists.},
  author={F Crofts and Shashank Rohatagi and Mar{\'i}a Teresa L. Pino and B DeLise and J Zhang and M Nguyen and Pierre Guittin and St{\'e}phane Barbellion and Pascale Brunel and Thomas Hofmann and J. Schmidt and Melisa Wong and Peter M. Lockey and Steven A. Lerman and Robert L Clark},
  journal={Birth defects research. Part B, Developmental and reproductive toxicology},
  year={2004},
  volume={71 2},
  pages={
          69-79
        }
}
  • F. Crofts, S. Rohatagi, R. Clark
  • Published 1 April 2004
  • Biology, Medicine
  • Birth defects research. Part B, Developmental and reproductive toxicology
BACKGROUND Integrins such as VLA-4 (Very late antigen 4, integrin alpha4beta1) play key roles in cell-cell interactions that are critical for development. Homozygous null knockouts of the VLA-4 alpha4-subunit or VCAM-1 (VLA-4 cell surface ligand) in mice result in failure of the allantois and chorion to fuse leading to interrupted placentation and cardiac development and embryo lethality. Embryo-fetal studies of three VLA-4 antagonists, IVL745, IVL984, and HMR1031 [Crofts et al., Birth Defects… 
Different embryo-fetal toxicity effects for three VLA-4 antagonists.
  • F. Crofts, M. Pino, R. Clark
  • Medicine, Biology
    Birth defects research. Part B, Developmental and reproductive toxicology
  • 2004
TLDR
Dramatic differences in teratogenic potential were observed: IVL745 was not ter atogenic, HMR1031 caused slight embryo-fetal effects at maternally-toxic doses, and IVL984 was a potent teratogen at doses where direct maternal toxicity was limited to abortions in rabbits.
Embryo/fetal development in cynomolgus monkeys exposed to natalizumab, an alpha4 integrin inhibitor.
TLDR
Natalizumab had no abortifacient or teratogenic effects, but was associated with changes in fetal hematopoiesis and leukocyte trafficking.
Teratogen update: Malaria in pregnancy and the use of antimalarial drugs in the first trimester
  • R. Clark
  • Medicine, Biology
    Birth defects research
  • 2020
TLDR
Limitations in the assessment of the safety of ACTs in the first trimester are a lack of exposures early in gestation, limited postnatal evaluation for cardiovascular malformations, and the pooling of all ACTs for the Assessment of risk.
Thoracic skeletal defects and cardiac malformations: a common epigenetic link?
TLDR
A model in which pregnant rats are treated with dimethadione is developed, suggesting a mechanistic link between cardiogenesis and skeletal development, and examines the hypothesis that posttranslational modifications of core histones may be altered by some developmental toxicants.
Very late antigen-4 integrin antagonists
TLDR
The present review summarizes work establishing natalizumab as an agent for the treatment of multiple sclerosis and Crohn's disease as well as the safety concerns caused by the development of progressive multifocal leukoencephalopathy in three patients during natalIZumab trials.
Maternal PUFAs, Placental Epigenetics, and Their Relevance to Fetal Growth and Brain Development
TLDR
An optimal level of maternal omega-3 (n-3) PUFAs may protect the placenta’s structural and functional integrity and allow fetal growth by controlling the aberrant placental epigenetic changes.
Concordance of preclinical and clinical pharmacology and toxicology of therapeutic monoclonal antibodies and fusion proteins: cell surface targets
TLDR
There was poor concordance for human pharmacodynamics in genetically deficient mice and for human adverse effects in all three test systems, and no evidence that NHPs have superior predictive value was found.
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Different embryo-fetal toxicity effects for three VLA-4 antagonists.
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  • Medicine, Biology
    Birth defects research. Part B, Developmental and reproductive toxicology
  • 2004
TLDR
Dramatic differences in teratogenic potential were observed: IVL745 was not ter atogenic, HMR1031 caused slight embryo-fetal effects at maternally-toxic doses, and IVL984 was a potent teratogen at doses where direct maternal toxicity was limited to abortions in rabbits.
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