Cystic fibrosis: Insight into CFTR pathophysiology and pharmacotherapy

Cystic fibrosis is the most common life-threatening recessively inherited disease in Caucasians. Due to early provision of care in specialized reference centers and more comprehensive care, survival has improved over time. Despite great advances in supportive care and in our understanding of its pathophysiology, there is still no cure for the disease. Therapeutic strategies aimed at rescuing the abnormal protein are either being sought after or under investigation. This review highlights salient insights into pathophysiology and candidate molecules suitable for CFTR pharmacotherapy. Clinical trials using Ataluren, VX-809 and ivacaftor have provided encouraging data. Preclinical data with inhibitors of phosphodiesterase type 5, such as sildenafil and analogs, have highlighted their potential for CFTR pharmacotherapy. Because sildenafil and analogs are in clinical use for other clinical applications, research on this class of drugs might speed up the development of new therapies for CF.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Despite great advances in supportive care, there is still no cure for CF. ► Therapeutic strategies aimed at rescuing the abnormal CFTR are under investigation. ► Clinical trials using Ataluren, VX-809 and ivacaftor have provided encouraging data. ► Preclinical data with sildenafil and analogs highlight their potential for CF therapy.