Published date: 6/3/2026

Value Proposition: Using CLCA1 VWA to specifically potentiate TMEM16A to enhance mucociliary transport in cystic fibrosis and other mucus obstructive diseases.

Technology Description

Researchers at Washington University in St. Louis have developed a potentiator, CLCA1 VWA (a small protein), that can specifically potentiate TMEM16A to enhance mucociliary transport in the cystic fibrosis (CF) airway and relieve thick mucus in other mucus obstructive diseases such as COPD. Chloride channel activity is critical for proper mucus function and mucociliary transport. This is exemplified in cystic fibrosis (CF) where different mutations in the CFTR gene cause dysfunction of the CFTR chloride channel, leading to thick, sticky mucus and impaired mucociliary transport. Current therapeutic approaches to resolve this involve developing small molecule correctors to correct CFTR (ivacaftor, lumacaftor, elexacaftor, tezacaftor), but this approach is genotype-specific and not effective for all patients.

This novel approach uses a unique composition of CLCA1 to bind to TMEM16A and potentiate, is universal of the CF genotype, and can be used to enhance mucociliary transport and as a supplement to treatments such as Trikafta.

Above figure: Shows that this specific potentiation can greatly enhance mucociliary transport in a human tissue model of the CF airway.

Stage of Research

Discovered CLCA1 specifically binds to and potentiates TMEM16A by increasing surface expression and identified that the CLCA1 VWA is the minimal region required to potentiate TMEM16A. Created CLCA1 VWA construct and showed it potentiates TMEM16A in primary CF airway cells, and benefited mucus function by enhancing MCT.

Publications

Berry KN, Brett TJ. Structural and Biophysical Analysis of the CLCA1 VWA Domain Suggests Mode of TMEM16A Engagement. Cell Rep. 2020 Jan 28;30(4):1141-1151.e3. doi: 10.1016/j.celrep.2019.12.059. Epub 2020 Jan 28. PMID: 31995732; PMCID: PMC7050472.

Applications

• Treatment for cystic fibrosis and other mucus-obstructive diseases

Key Advantages

• Approach can be used regardless of CFTR genotype

• Enhances mucociliary transport

Patents

Patent application filed

Related Web Links – Thomas Brett Profile; Brett Lab