Pharmacological Potential of PDE5 Inhibitors for the Treatment of Cystic Fibrosis

Abstract

Recent basic research has aroused great interest in the therapeutic potential of phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, vardenafil and taladafil, for the treatment of cystic fibrosis (CF). CF is the most common, life-threatening, recessively inherited disease in Caucasian populations. An estimated 1 in 2,500 Caucasian live births are affected and approximately 80,000 people in the world are diagnosed with CF. Due to mutation in the CF transmembrane conductance regulator (CFTR) gene [1,2], which encodes the main chloride channel expressed in epithelia, CF causes abnormal mucociliary clearance mainly in the lungs, leading to a vicious cycle of obstruction/infection/inflammation that progressively and irreversibly damages the lung tissue and architecture. Although many organs are affected in CF, pulmonary disease is the major cause of morbidity and mortality [3,4]. Despite more than two decades of intensive investigation of the genetics [1,2], pathophysiology and clinical phenotypes of CF [3,4], there is still no cure for CF. As a matter of fact, therapies have been limited to alleviating clinical manifestations. Although life expectancy and quality of life have progressively improved, CF continues to inflict major burdens and to shorten lives.