In cystic fibrosis (CF), mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause either insufficient or dysfunctional CFTR protein to be created. The CFTR protein typically allows chloride to enter and exit lung cells, helping to regulate fluids on the cell surface. Without functioning CFTR, there is insufficient chloride to attract these fluids, resulting in thick, sticky mucus that leads to lung infections.
The Cystic Fibrosis Foundation has awarded up to $7 million to Enterprise Therapeutics to develop a compound that increases the activity of another chloride channel in lung cells, TMEM16A. By targeting the TMEM16A channel, Enterprise hopes the drug will help hydrate the mucus in the CF lung, making it easier to clear and thereby reduce the incidence of lung infections.
The award supports preclinical development of the drug ETD002 in the lab and -- if successful -- testing in people with CF in clinical trials. ETD002 could help all people with CF regardless of their mutation.
Researchers believe that non-CFTR chloride channels can possibly provide the chloride flow lost in people with CF due to their reduced or dysfunctional CFTR. TMEM16A is a calcium activated chloride channel (CaCC) which opens in response to small increases in calcium inside the lung cells. Enterprise's small-molecule drug makes the CaCC channel more sensitive to small increases in calcium within the cells, thereby activating the channel for longer and allowing more chloride to flow across the cell membrane. The increased flow would help hydrate the mucus in the lungs, making it easier to cough out and decreasing the likelihood of infections.
For more information on this study, please see the Enterprise press release.