Researchers discover precisely how thalidomide causes birth defects

April 19, 2011

Thalidomide may have been withdrawn in the early 1960s for use by pregnant women, but its dramatic effects remain memorable half a century later.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."

Explore further: Japan may regulate thalidomide

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

Related Stories

Japan may regulate thalidomide

June 13, 2006

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

New insights into thalidomide-birth defect episode

November 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 ...

Solving the 50-year-old puzzle of thalidomide

November 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 ...

Japan team uncovers thalidomide mystery

March 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 use for once-cursed drug Thalidomide?

April 4, 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

Basic research fuels advanced discovery

August 26, 2016

Clinical trials and translational medicine have certainly given people hope and rapid pathways to cures for some of mankind's most troublesome diseases, but now is not the time to overlook the power of basic research, says ...

New method creates endless supply of kidney precursor cells

August 25, 2016

Salk Institute scientists have discovered the holy grail of endless youthfulness—at least when it comes to one type of human kidney precursor cell. Previous attempts to maintain cultures of the so-called nephron progenitor ...

New avenue for understanding cause of common diseases

August 25, 2016

A ground-breaking Auckland study could lead to discoveries about many common diseases such as diabetes, cancer and dementia. The new finding could also illuminate the broader role of the enigmatic mitochondria in human development.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.