![]() ![]() This study aimed to evaluate the safety profile of ivacaftor in a larger CF population (ie, subjects homozygous for the F508del-CFTR mutation). 11 Ivacaftor was tested for up to 4 weeks in a small number of subjects with CF who had the G551D-CFTR mutation on at least one CFTR allele 12 and has been approved in the United States for the treatment of CF in patients who are ≥ 6 years of age and have a G551D mutation. 10 G551D-CFTR (c.1652G > A) is the most common gating mutation associated with CF disease, having an allelic frequency of only approximately 2.2%. ![]() 9 Ivacaftor is a CFTR potentiator shown to increase chloride transport by activated CFTR channels at the cell surface in vitro. 9Ĭompounds designed to increase CFTR channel opening, CFTR potentiators, can prevent the hyperabsorption of water across the epithelial surface. 7, 8 Furthermore, any F508del-CFTR protein reaching the cell surface may also have a defect in the opening and closing of the channel, known as a gating defect. ![]() 6 The F508del-CFTR mutation causes improper protein folding, resulting in little or no CFTR protein reaching the cell surface. 3‐ 5 Approximately 90% of patients with CF in North America have F508del on at least one allele, and nearly one-half are homozygous. 2 The most prevalent disease-causing CFTR mutation is F508del (c.1521_1523delCTT). 1 Inadequate airway hydration results in obstruction of the airways with thick mucus, rendering the airways vulnerable to chronic infection and inflammation, leading to irreversible structural changes and respiratory failure.ĬF-causing CFTR mutations cause either diminished or defective CFTR protein in the apical membrane, resulting in decreased chloride transport. The encoded protein, CFTR, is an epithelial chloride channel that maintains hydration of lung secretions by regulating water absorption. Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene. ![]()
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