Question

What is the developmental defect associated with Thalidomide? What was it prescribed for? What is the molecular mechanism?

Answer 1

Thalidomoide is an Immunomodulatory Drug or Antiangiogenic Drug.

It is a Sedative drug and was prescribed for pregnant women in order to relieve pregnancy nausea.

Now Thalidomide is Only prescribed in very few cases like

a) Hansen's disease( leprosy)

b)multiple myeloma.

Use of Thalidomide was responsible for Many Devolopmental abnormalities or teratogenesis.

Deveolpmental Defects Associated with thalidomide are-

1.Absence of the auricles --Leading to Deafness

2.Defects in Lower Limb (femur and of the tibia)

3.Defects in Upper limbs-Hypoplasia or Absent Limbs

4.Thumbs with three joints.

5.Defects in eye muscles and facial Muscles.

6.Malformations in heart,bowel,uterus and gallbladder.

Mechanism of action of thalidomide-

The drug displaces the complex ( protein complex CD147 and MCT1-2 Proteins that  promote proliferation, metabolism & formation of new blood vessels in cancers ) from its binding to cereblon through which these actions are mediated.

Molecular mechanism by Which Thalidomide causes teratogenicity involves-

1.Oxidative Stress-------Oxidative damge to DNA -------Programmed cell death.

2.Anti angionenesis ----Down regulation of growth Factors & Cell death-----Mesenchymal Loss ----Cell death

3.Thalidomide- Binds to thalidomide Binding Protein-cereblon-------------Inhibts ubiquitin ligase activity---Accumulation of Unknwon toxic Substances------Down regulation-------teratogenesis