Thalidomide and birth defects

Lucas Fraga, Alex Diamond, Neil Vargesson

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Abstract

Thalidomide is a teratogenic drug that caused horrific birth defects when prescribed as an antiemetic to pregnant women in the 1960s. The most stereotypical defect is symmetrical limb malformations such as phocomelia, although ear, eye and internal organ defects are also observed. Thalidomide was consequently withdrawn from the market. However, Thalidomide has since been shown to have many beneficial antiinflammatory and immunomodulatory effects, and is therefore used in a regulated manner in the treatment against cancers and inflammatory disorders. Sadly, new cases of babies being born affected by thalidomide, likely due to medicine sharing, are reported in Brazil. The mechanisms of how thalidomide causes a wide range of embryonic malformations are becoming clearer; thalidomide is thought to act through molecules such as cereblon and tubulin and also affects blood vessel development and cell death, resulting in teratogenesis. Fully understanding the molecular events induced by thalidomide is essential if we are to develop a safe but clinically relevant form of the drug.
Original languageEnglish
Article numbera0026052
Pages (from-to)1-11
Number of pages11
JournaleLS
VolumeJanuary 2016
Early online date15 Jan 2016
DOIs
Publication statusPublished - 2016

Bibliographical note

Apologies to the many papers we were unable to cite, due to space constraints. We
thank Lynda Erskine, Shaunna Beedie and Chris Mahony for helpful discussions. Lucas Rosa Fraga is funded by a PhD scholarship from the Science without Borders program - CNPq Brazil - INAGEMP/ Grant CNPq 573993/2008-4. Alex J. Diamond is funded by a BBSRC DTP PhD Scholarship.

Keywords

  • angiogenesis
  • cell death
  • cereblon
  • reactive oxygen species
  • time sensitive window
  • mechanisms of tetragenosis
  • chicken embryo
  • zebrafish embryo

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