Cystic fibrosis airway inflammation enables elexacaftor/tezacaftor/ivacaftor-mediated rescue of N1303K CFTR mutation

Martina Gentzsch; Brooke Baker; Deborah M Cholon; Charissa W Kam; Cameron J McKinzie; Katherine A Despotes; Susan E Boyles; Nancy L Quinney; Charles R Esther Jr; Carla M P Ribeiro

doi:10.1183/23120541.00746-2023

Cystic fibrosis airway inflammation enables elexacaftor/tezacaftor/ivacaftor-mediated rescue of N1303K CFTR mutation

ERJ Open Res. 2024 Jan 15;10(1):00746-2023. doi: 10.1183/23120541.00746-2023. eCollection 2024 Jan.

Authors

Martina Gentzsch^{1

2

3

4}, Brooke Baker^{5

4}, Deborah M Cholon¹, Charissa W Kam⁶, Cameron J McKinzie⁶, Katherine A Despotes², Susan E Boyles¹, Nancy L Quinney¹, Charles R Esther Jr^{1

2

7}, Carla M P Ribeiro^{1

3

8

7}

Affiliations

¹ Marsico Lung Institute and Cystic Fibrosis Research Center, The University of North Carolina, Chapel Hill, NC, USA.
² Department of Pediatrics, The University of North Carolina, Chapel Hill, NC, USA.
³ Department of Cell Biology and Physiology, The University of North Carolina, Chapel Hill, NC, USA.
⁴ Joint first authors.
⁵ Department of Pharmacy, Duke University Medical Center, Durham, NC, USA.
⁶ Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC, USA.
⁷ Joint senior authors.
⁸ Department of Medicine, The University of North Carolina, Chapel Hill, NC, USA.

Abstract

Rescue of N1303K CFTR by highly effective modulator therapy (HEMT) is enabled by CF airway inflammation. These findings suggest that evaluation of HEMT for rare CFTR mutations must be performed under inflammatory conditions relevant to CF airways. https://bit.ly/3tTcoJE.

Grants and funding

P30 DK065988/DK/NIDDK NIH HHS/United States