Potential drug target for cystic fibrosis identified
Washington: Researchers have discovered a gene called DGKi as a new target for drug development for cystic fibrosis.
The study by scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg and Regensburg University, both in Germany, and the University of Lisboa, in Portugal, also uncovered a large set of genes not previously linked to the disease, demonstrating how a new screening technique can help identify new drug targets.
In patients with cystic fibrosis, the mutations to CFTR render it unable to carry out its normal tasks. Among other things, this means CFTR loses the ability to control a protein called the epithelial sodium channel (ENaC).
Starting with a list of around 7000 genes, the scientists systematically silenced each one, using a combination of genetics and automated microscopy, and analysed how this affected ENaC.
They found over 700 genes which, when inhibited, brought down ENaC activity, including a number of genes no-one knew were involved in the process. Among their findings was a gene called DGKi. When they tested chemicals that inhibit DGKi in lung cells from cystic fibrosis patients, the scientists discovered that it appears to be a very promising drug target.
"Inhibiting DGKi seems to reverse the effects of cystic fibrosis, but not block ENaC completely. Indeed, inhibiting DGKi reduces ENaC activity enough for cells to go back to normal, but not so much that they cause other problems, like pulmonary oedema," Margarida Amaral from the University of Lisboa said.
These promising results have already raised the interest of the pharmaceutical industry and led the researchers to patent DGKi as a drug target, as they are keen to explore the issue further, searching for molecules that strongly inhibit DGKi without causing side-effects.
The study is published in journal Cell.
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