The Curious Clinicians 83 - Thalidomide Embryopathy
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Jan 31, 2024 The podcast explores the history and mechanisms of thalidomide, a teratogen that caused birth defects in thousands of babies. Topics covered include the development and marketing of thalidomide, the devastating impact on pregnant women, the mechanisms of thalidomide embryopathy, and the contrasting actions of individuals in drug regulation.
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Thalidomide's Global Impact
- Over 10,000 babies globally suffered severe birth defects due to thalidomide use in pregnancy during the late 1950s and early 1960s.
- The drug was aggressively marketed as totally safe for pregnant women despite devastating effects becoming clear after five years.
Ubiquitin Ligase Disruption in Embryopathy
- Thalidomide disrupts embryonic limb growth mainly by binding cereblon and blocking ubiquitin ligase function, impairing fibroblast growth factor expression.
- This mechanism was proven when chick embryos with mutated cereblon resistant to thalidomide exposure developed normally.
Oxidative Stress Mechanism
- Thalidomide generates reactive oxygen species causing oxidative DNA damage to embryos, contributing to limb defects.
- Administering a free radical scavenger alongside thalidomide nearly prevented these malformations in rabbit models.