Deformity-causing mechanism of drug Thalidomide discovered

By ANI
Saturday, March 13, 2010

LONDON - The primary mechanism by which thalidomide causes malformed limbs in developing embryos has been discovered by scientists at Tokyo Institute of Technology.

The drug’s side-effect gained recognition after many affected children were born to mothers who had been prescribed the drug for morning sickness.

According to research in the journal Science, thalidomide binds to and renders inactive the protein cereblon, which is very important in limb formation.

Drug thalidomide may be effective in the treatment of certain cancers and leprosy, but the fact that it causes birth defects means that for women its use remains risky and controversial.

In the study, the research team, led by Takumi Ito from the Tokyo Institute of Technology in Japan, isolated the negative effects of the “potentially useful” drug.

They set out to discover which target molecules thalidomide bound to in the body. They did this using tiny beads that extracted each individual molecule the drug bound to.

The conclusion was confirmed after the usage of genetic techniques to reduce the production of the cereblon protein in developing zebrafish and chick embryos. The embryos with reduced cereblon had similar developmental defects to those that were treated with thalidomide.

“We [have shown] that cereblon… is a primary target of thalidomide teratogenicity” (or its ability to cause birth defects), the researchers wrote in their Science article.

Dr Ito told BBC News: “Although the mechanism for the teratogenic effect was made clear, the mechanism for its therapeutic effects remains unknown.

“[If we want to develop] a new drug devoid of teratogenic activity, it is important to understand [this] mechanism… this is what we are heading for.” (ANI)

Filed under: Science and Technology

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