Mechanism behind thalidomide's toxicity
Scientists believe they have pinpointed why thalidomide causes birth defects when given to pregnant women.
There have been many theories as to why thalidomide caused limb defects when it was used to combat morning sickness; however few have had enough data to back the ideas up. The problem with studying thalidomide is that the drug is broken down into over 100 different compounds as it passes through the liver.
This new study identified and isolated many of these compounds for the first time, allowing them to be tested in chickens. The team found a compound that was similar to a thalidomide breakdown product in both its structure and chemical composition. This compound, CPS49, was administered to the chickens at a similar point as when thalidomide was given to pregnant women.
The results showed that CPS49 caused severe limb defects, leaving the rest of the embryo untouched. They conclude that this is because the embryos core blood vessels were suitably developed at the time, but the limbs had not yet acquired an adequate blood supply. This paper therefore puts the ability of thalidomide to block the development of new blood vessels as the most likely cause of its side effects.
The aim is to produce a compound similar to thalidomide without the side effects, as it is currently an important therapeutic in the treatment of leprosy and multiple myeloma, a form of cancer.