Cystic fibrosis is an inherited disease caused by a single gene mutation. The mutation causes multiple organ lesions, most notably an abnormal thickening of secretions in the lungs. This can lead to recurrent lung infections, making it difficult for patients to breathe and affecting their lives and health. Recently, researchers from the University of Heidelberg and other institutions in Germany have discovered a promising drug for the treatment of cystic fibrosis. In addition, they have identified a large number of previously unknown cystic fibrosis-related genes. This suggests that novel screening techniques will help develop new drug targets. The research paper was published in the recent issue of Cell. CFTR deficiency in patients with cystic fibrosis leads to abnormal excitation of the epithelial sodium channel (ENaC), causing excessive sodium ion accumulation in the patient’s lungs, which attracts water molecules and therefore leads to increasing mucus in the patient’s lungs, making the lungs dehydrated. Currently, the only treatment available is for CFTR mutations, but it is only effective in one third of patients. So if you want to treat cystic fibrosis more effectively, you should look for drugs that act on ENaC rather than trying to correct the CFTR mutation. Unfortunately, however, most of the drugs that inhibit ENaC are used to treat hypertension, not cystic fibrosis. In this latest study, scientists used other approaches to treat cystic fibrosis. The researchers hope to screen for effective drugs to downregulate a gene that will allow ENaC to be suppressed. The scientists used genetic techniques and automated analysis to systematically suppress more than seven thousand genes one by one, analyzing which mutations affect ENaC. They found that downregulation of more than seven hundred genes suppressed ENaC activity, including many previously unknown genes. One of these genes is called DGKi, and the scientists tested a drug to inhibit DGKi function in lung cells and found that the drug was highly effective. Researchers say that inhibiting DGKi appears to significantly reverse cystic fibrosis, but does not completely inhibit ENaC function. In fact, inhibition of DGKi reduced ENaC activity enough to bring the cells to normal levels without producing other side effects such as pulmonary edema. This finding has attracted the interest of pharmaceutical companies to further develop new drugs using DGKi as a target.