Cause of thalidomide deformities revealed

Japanese Scientists believe they have discovered one of the vital molecular targets that bind to thalidomide to cause birth defects. The finding could enable new drugs to be developed that are identical to thalidomide - which is effective in treating Hansen’s disease and certain cancers - but without the terrible side effects on the developing embryo. 

The Scientists attached thalidomide to magnetic beads and exposed the immobilised drug to extracts of cells. They found that cereblon, a protein, bound to the thalidomide. Cereblon's activity is mainly important in limb development.

The team then genetically engineered chicks and zebrafish so that they lacked this protein. Embryos that subsequently developed had similar limb defects to those caused by thalidomide. They also engineered organisms to have a mutated version of the protein which was unable to bind to thalidomide. In these animals the drug did not cause developmental defects in embryos.

Together, these findings suggest that cereblon needs to be present and functioning to ensure healthy development of the embryo, and that thalidomide interferes with its ability to do this.

 The work provides a crucial step towards understanding the mechanism of action of thalidomide, which could lead to the development of similar drugs that do not interfere with cereblon.