Antibodies to treat a few genetic diseases:

Antibodies to treat a few genetic diseases:


  • A team of researchers led by Prof. Arun Shukla from the Department of Biological Sciences and Bioengineering at the Indian Institute of Technology (IIT), Kanpur, seems to have found a way to treat the Inherited genetic diseases such as retinitis pigmentosa and nephrogenic diabetes.

What is Retinitis pigmentosa?

  • Retinitis pigmentosa is an inherited, degenerative eye disease that leads to progressive loss of vision as one gets older.

What is genetic nephrogenic diabetes?

  • Genetic nephrogenic diabetes arises from kidney cells’ inability to retain water leading to extreme thirst and dehydration.

What are the causes behind it?

  • The cause of disease is a mutation in the G-protein-coupled receptors (GPCR) which causes the receptors to be pulled from the plasma membrane to the inside of the cell just as the receptors reach the cell membrane to start signalling.
  • In the absence of the receptors (rhodopsin GPCR in the case of retinitis pigmentosa and vasopressin GPCR for genetic nephrogenic diabetes) the cells fail to signal and do not function normally.

How does it function?

  • They have designed synthetic antibody fragments which specifically bind to beta-arrestins at the position where clathrin gets bound.
  • The antibodies therefore, prevent the clathrin protein from binding to beta-arrestins. It further prevents endocytosis.
  • The pulling in or trafficking of the G-protein-coupled receptors (GPCR) receptors from the membrane surface to inside the cells (which is called endocytosis) happens when a small family of proteins called beta-arrestins bind to GPCR receptors and to another class of proteins called clathrin.
  • Trying to prevent the trafficking of the GPCR receptors from the membrane surface to inside the cells is like turning the clock back.
  • Rhodopsin and Vasopressin receptors would stay intact on the cell membrane and will start signalling and thus enabling the otherwise mutant cells to function normally.
  • The designer proteins created by the research team will provide unexplored territory for therapeutic applications for inherited diseases.

What next?

  • Since the mechanism of the two diseases is the same, the antibodies can work equally well immaterial of the cell type involved.
  • The next step will be to develop new strategies to deliver the antibodies into human live cells and animal models.
  • The big advantage of using antibodies is that they selectively block receptor endocytosis but not signalling. This provides a unique handle, currently not available anywhere in the world, for targeting a specific GPCR function.
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