A “promising” new drug for cystic fibrosis has been revealed by scientists at the European Molecular Biology Laboratory.
The disease, which causes life-threatening lung infections, is a hereditary disease caused by mutations in the CFTR gene that leads to it losing its ability to control a protein called the epithelial sodium channel (ENaC), which causes the cells in the lungs to absorb too much sodium and creates a thick mucus.
The only drug available that counteracts a cystic fibrosis-related mutation only works on the 3% of patients that carry one specific mutation out of the almost 2,000 CFTR mutations discovered so far.
But this latest study, which is published in Cell shows that a more promising therapy could soon be available.
Scientists at Heidelberg and Regensburg universities, both in Germany, and the University of Lisboa, Portugal, used a combination of genetics and automated microscopy to analyse how ENaC was affected when they shut down each of the 7,000 genes.
They found more than 700 genes which, when restricted, reduced ENaC activity. These included a number of genes that were not known to be involved in the process.
When the chemicals in a gene called DGKi were tested, the scientists found it to be a promising treatment.
“Inhibiting DGKi seems to reverse the effects of cystic fibrosis, but not block ENaC completely,” explains Margarida Amaral from the University of Lisboa.
“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.”
Karl Kunzelmann from Regensburg University said even though it was early days for the research, the results were “encouraging”.
“We have DGKi in our cells because it is needed, so we need to be sure that these drugs are not going to cause problems in the rest of the body,” he adds.
Almaça J et al. High-Content siRNA Screen Reveals Global ENaC Regulators and Potential Cystic Fibrosis Therapy Targets. Cell 12th September 2013. DOI: 10.1016/j.cell.2013.08.045.
Leave a Reply