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.
Louvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Centre des Sciences de Santé, Université catholique de Louvain, Ave Hippocrate 10, B-1200 Brussels, Belgium.
Bob
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Lubamba
Barbara
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Dhooghe
Sabrina
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Noel
Teresinha
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Leal
D000818:Animals; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D058990:Molecular Targeted Therapy
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator