How Thalidomide causes birth defects

A current study in Science from the Tokyo Institute of Technology seems to demonstrate how Thalidomide causes birth defects. Here’s the abstract from the paper:

Half a century ago, thalidomide was widely prescribed to pregnant women as a sedative but was found to be teratogenic, causing multiple birth defects. Today, thalidomide is still used in the treatment of leprosy and multiple myeloma, although how it causes limb malformation and other developmental defects is unknown. Here, we identified cereblon (CRBN) as a thalidomide-binding protein. CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks. Thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting the associated ubiquitin ligase activity. This study reveals a basis for thalidomide teratogenicity and may contribute to the development of new thalidomide derivatives without teratogenic activity.

Source:

Ito et al 2010. Identification of a Primary Target of Thalidomide Teratogenicity. Science. Vol. 327. no. 5971, pp. 1345 – 1350. Link

Comments

  1. #1 daedalus2u
    March 12, 2010

    Maybe. But thalidomide interferes with NO signaling too.

    http://www.ncbi.nlm.nih.gov/pubmed/19912234

    I suspect that is how thalidomide causes autism in a very narrow time window.

  2. #2 I.N.
    March 25, 2010

    Birth defects occur during fetal development. Most of them appear in the first trimester and alter the aspect and the functionality of the body. Various organs are affected( brain and head malformations, heart, lungs, liver, digestive system) and also bones.

Current ye@r *