TMEM16A was recently identified as a calcium-activated chloride conductance and a key orchestrator of anion secretion in the human airway epithelium (Caputo et al 2008; Schroeder et al 2008; Yang et al 2008). It is now clinically established that promoting anion secretion in the airway leads to enhanced mucus clearance and reduced exacerbation frequency in CF patients and as such TMEM16A represents an important target for the next generation of mucokinetics. Importantly, positive regulators of TMEM16A function will be expected to be of benefit in all CF patients, irrespective of their CFTR mutational status.
A screen of microbial-derived products using a 3D model of the human airway epithelium (bronchospheres) revealed flagellin (FLG) as a potential regulator of mucociliary structure and function. Flagellin, a TLR5-agonist, is the key protein component of bacterial flagella expressed by a number of organisms including Pseudomonas aeruginosa. Considering that mucus plugs in the airways of many cystic fibrosis (CF) patients would be reasonably expected to contain FLG, the epithelium is likely to be chronically exposed to this bacterial protein.
Enterprise Therapeutics is a drug discovery company dedicated to the research and development of novel therapies for the treatment of respiratory diseases. The company is based in the UK with offices at the Sussex Innovation Centre.
- Enterprise Therapeutics publishes paper on novel therapeutic approach for treatment of all cystic fibrosis patientsJanuary 8, 2020 - 10:16 am
- TMEM16A Channel Function Does Not Influence Goblet Cell Numbers or Mucin Secretion In The Human Airway Epithelium – NACFC – Nashville – October 2019November 7, 2019 - 5:32 pm
- EACT Increases Intracellular Calcium Levels by a Tmem16a-Independent Mechanism – NACFC – Nashville – October 2019November 7, 2019 - 5:30 pm
- The In Vitro & In Vivo Pharmacology of Novel Tmem16a Potentiator Compounds – NACFC – Nashville – October 2019November 7, 2019 - 5:29 pm
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Is there a need for new modulators in #cysticfibrosis? Our research demonstrates the first pre-clinical proof of #TMEM16A potentiation as a novel approach for the treatment of all #CF patients, read further discussion on this topic at @atscommunity: http://bit.ly/2QP7eIT