Researchers discover precisely how thalidomide causes birth defects

Thalidomide may have been withdrawn in the early 1960s for use by pregnant women, but its dramatic effects remain memorable half a century later. Now, researchers have taken a major step toward understanding exactly how thalidomide causes the birth defects. This is important as thalidomide is still used to treat diseases like multiple myeloma and leprosy, and is being tested for cancers and autoimmune disorders. This discovery was recently published online in the FASEB Journal.

"The ability of breakdown products to cause birth defects complicates our attempts to understand how the birth defects arise and the search for safer alternatives to thalidomide, although the rabbit embryo culture model will facilitate both processes," said Peter G. Wells, Pharm.D., a researcher involved in the work from the Department of Pharmacology and Toxicology at the University of Toronto in Ontario, Canada.

Specifically, Wells and colleagues found that birth defects result from not only thalidomide, but also from the compounds that it breaks down to in the body, which last up to 40 times longer in the body than thalidomide itself. These compounds ultimately lead to the production of highly toxic forms of oxygen, called "reactive oxygen species," (ROS) including hydrogen peroxide and free radicals that alter disrupt normal , causing birth defects.

To make this discovery, the scientists developed a new for fetal thalidomide exposure by extracting rabbit embryos from pregnant mothers during the first trimester of pregnancy, when the limbs and other structures are developing. Then they cultured the embryos in dishes for one to two days, with or without exposure to thalidomide or one of its breakdown products. Front and hind limb deformities as well as other abnormalities were observed only in the embryos exposed to thalidomide or one of its products. caused by ROS and was similarly increased only in the exposed embryos.

"Administering thalidomide to pregnant women remains was of the biggest mistakes made in modern medicine," said Gerald Weissmann, M.D., Editor-in-Chief of the , "Yet we now use thalidomide and related products as effective therapies for serious diseases. This research not only explains what caused all that misery years ago, but promises to help us find safer alternatives to thalidomide in the future."

More information: Crystal J. J. Lee, Luisa L. Gonçalves, and Peter G. Wells. Embryopathic effects of thalidomide and its hydrolysis products in rabbit embryo culture: evidence for a prostaglandin H synthase (PHS)-dependent, reactive oxygen species (ROS)-mediated mechanism. FASEB J. doi:10.1096/fj.10-178814

add to favorites email to friend print save as pdf

Related Stories

Japan team uncovers thalidomide mystery

Mar 12, 2010

Japanese scientists have uncovered how thalidomide led to deformities in children born to mothers taking the drug in the 1950s and 1960s, according to a study released Friday.

New insights into thalidomide-birth defect episode

Nov 10, 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 ...

Japan may regulate thalidomide

Jun 13, 2006

Doctors in Japan will be required to register patients who are using the drug thalidomide under proposed regulations, the Japan Times reported.

Solving the 50-year-old puzzle of thalidomide

Nov 17, 2009

Research into the controversial drug thalidomide reveals that the mechanism through which the drug causes limb defects is the same process which causes it to damage internal organs and other tissues. The article, published ...

New use for once-cursed drug Thalidomide?

Apr 04, 2010

Thalidomide, the sedative blamed for tragic birth defects half a century ago, treated a rare inherited blood disorder, according to lab experiments reported on Sunday.

Recommended for you

A better way to track emerging cell therapies using MRIs

Sep 19, 2014

Cellular therapeutics – using intact cells to treat and cure disease – is a hugely promising new approach in medicine but it is hindered by the inability of doctors and scientists to effectively track the movements, destination ...

User comments