November 5, 2008 — Scientists in Germany
have discovered why the medication thalidomide appeared safe in animal tests
before going on the market 50 years ago, only to cause perhaps the most
extensive outbreak of drug-induced birth defects in medical history. Their study
is scheduled for the December 1 edition of ACS’ Molecular Pharmaceutics, a bimonthly
Jurgen Knobloch, Ulrich Ruther and
colleagues note that more than 10,000 children were born with severe birth
defects after drug regulators in Europe
approved the medication for treating nausea and vomiting in pregnant women. The
drug, never approved for that use in the United
States, is available for certain conditions,
including multiple myeloma and leprosy. The birth defects outbreak puzzled
scientists because pre-marketing tests in lab mice and rats showed no sign of a
birth defect risk.
researchers point out that those animals proved to be resistant to thalidomide’s
adverse effects, and in the new study they describe discovery of the biochemical
basis for that resistance. It involves a key difference between human embryonic
cells and those of mice. They found in mice cells advanced antioxidant defenses
compared to those in humans and other thalidomide-susceptible species.
Therefore, thalidomide is not able to induce the generation of large quantities
of damaging free radicals called superoxides in mouse embryonic cells as it does
in human embryonic cells (where subsequent cell death is believed to be
responsible for birth defects.)
News release courtesy of American Chemical Society.