Cystic Fibrosis is a debilitating and devastating respiratory disease

In May, Cystic Fibrosis Awareness Month, we aim to highlight some of the pioneering work on this often debilitating and devastating respiratory disease.

Prof. David Sheppard’s lab at the University of Bristol has long been a leading light in CF research. The Sheppard lab recently published seminal research characterizing the reduced chloride conductance in two rare CFTR mutant channels (S1159F and S1159P) that lead to Cystic Fibrosis.

Using single channel recordings Dr. Hongyu Li and collaborators across the world showed that these mutant channels have greatly reduced open probability (Po). Most CFTR mutant channels with reduced Po can be corrected by Vertex Pharmaceuticals’ CFTR potentiating compound VX770 (ivacaftor; or the triple medication trikafta, comprising ivacaftor, elexacaftor, tezacaftor), giving benefits to 90% of CF patients. However, Li et al. show that these two rare CFTR mutants would not be sufficiently potentiated by ivacaftor (or trikafta).

Consequently, Li et al.’s in vitro study provides vital evidence for a lack of translation for ivacaftor in CF patient populations carrying these CFTR mutant channels. These in vitro recordings have potential as a drug discovery assay to find new, alternative compounds that may potentiate and correct the channels to give CF patients therapeutic relief.

Contextualizing this study, Prof. Sheppard notes:

"As the Cystic Fibrosis Trust marks its 60th anniversary, it is appropriate to reflect on the progress made towards delivering the best possible care for people with cystic fibrosis. Evidence-based medicine has led to progressive improvements in the health of people with cystic fibrosis, while elexacaftor-tezacaftor-ivacaftor has transformed the outlook for many, but not all people with cystic fibrosis. This incentivises the cystic fibrosis community to do more, quicker to bring life-changing therapies to all people with cystic fibrosis. I am especially grateful to my colleagues past and present for their commitment and dedication to cystic fibrosis research and the Cystic Fibrosis Trust for funding our work"

— David Sheppard, professor at University of Bristol, United Kingdom

Congratulations to Hongyu Li and collaborators on this groundbreaking study.

Download the paper here
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