Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians, affecting more than 100,000 individuals worldwide. It is caused by pathogenic variants in the gene encoding CFTR, an anion channel at the plasma membrane of epithelial and other cells. Many CF pathogenic variants disrupt the biosynthesis and trafficking of CFTR or reduce its ion channel function. The most frequent mutation, loss of a phenylalanine at position 508 (F508del), leads to misfolding, retention in the endoplasmic reticulum, and premature degradation of the protein. The therapeutics available for treating CF lung disease include antibiotics, mucolytics, bronchodilators, physiotherapy, and most recently CFTR modulators. To date, no cure for this life shortening disease has been found. Treatment with the Triple combination drug therapy, TRIKAFTA®, is composed of three drugs: Elexacaftor (VX-445), Tezacaftor (VX-661) and Ivacaftor (VX-770). This therapy, benefits persons with CF, improving their weight, lung function, energy levels (as defined by reduced fatigue), and overall quality of life. We examined the effect of combining LAU-7b oral treatment and Triple therapy combination on lung function in a F508deltm1EUR mouse model that displays lung abnormalities relevant to human CF. We assessed lung function, lung histopathology, protein oxidation, lipid oxidation, and fatty acid and lipid profiles in F508deltm1EUR mice.

Czech Advanced Technology and Research Institute Palacky University Olomouc Czechia

Department of Biomedical Engineering McGill University Montreal QC Canada

Department of Physiology McGill University Montreal QC Canada

Faculty of Medicine McGill University Montreal QC Canada

Infectious Diseases and Immunity in Global Health Research Institute of the McGill University Health Centre Montreal QC Canada

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University Olomouc Czechia

Laurent Pharmaceuticals Montreal QC Canada

Meakins Christie Laboratories The Centre for Respiratory Research at McGill University and the Research Institute of the McGill University Health Centre Montreal QC Canada

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