Solving a 50-Year Mystery: How Thalidomide Causes Birth Defects

By Rachel Cernansky | May 12, 2009 3:51 pm

thalidomideResearchers may have finally figured out the mechanism of the tragic birth defects caused by thalidomide, the drug taken by pregnant women in the late 1950s as a remedy for nausea: It is thought to have inhibited development of new blood vessels at a crucial stage in the pregnancy.

Women usually took the drug at about five to nine weeks into their pregnancy to combat morning sickness, a specific window that lead researcher Neil Vargesson says “is crucial as that is when the limbs of babies are still forming…. The blood vessels involved in this process, at this stage of pregnancy, are still at an immature stage when they rapidly change and expand to accommodate the outgrowing limb” [BBC]. The most common birth defects caused by thalidomide were babies born with stunted or malformed limbs.

The drug has been difficult to study until now because the compound has to be metabolically activated in the liver, where it is broken down into potentially more than 100 different compounds. Each of those — or some combination — could be the cause of deformed limbs [Nature News]. But the research team found a way to isolate the drug’s metabolites and identified one compound, CPS49, that causes severe limb defects and blocks growth of new blood vessels.

When CPS49 was given to chicks (chosen because chickens are one of few lab animals in which thalidomide causes birth defects) at a stage of development corresponding to that at which thalidomide was often used in pregnant women, the compound selectively affected limb development, leaving the rest of the embryo untouched. This is because at that time blood vessels in the body of the embryo are relatively mature, says Vargesson, whereas vessels in the limbs are just beginning to form [Nature News]. Additionally, the team found that the embryos died when the compound was administered at an earlier developmental stage, while the limb defects were less severe when administered later on in development.

Pulled from the market in 1961, thalidomide caused approximately 10,000 children to be born with deformed limbs, brain defects, or other developmental deformities. Because use of thalidomide has picked up again to treat leprosy and multiple myeloma (a type of cancer), it is hoped that the new study, published in the Proceedings of the National Academy of Sciences, could contribute to the development of a similar drug that does not have the same side effects.

Related Content:
80beats: Chemicals That Warp Male Reproductive System Should Be Studied as a Group
DISCOVER: Works in Progress looks at thalidomide’s uses in fighting leprosy and other diseases

Image: Flickr / otisarchives3

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