Future challenges in cystic fibrosis treatment: focus on disease-modifying therapies

Cystic fibrosis (CF) is an autosomal recessive disorder due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to abnormality of chloride channels in mucus and sweat producing cells. Respiratory and gastrointestinal systems are primarily involved but eventually multiple organs are affected leading to life threatening complications. Genetic mutations in CFTR affect its synthesis, processing, and transport to the plasma membrane and/or impede its function as a chloride channel and conductance regulator. Research is proceeding on multiple fronts including inhalational agents, anti-inflammatory treatments, and pancreatic replacement therapies. Furthermore, improved understanding of the molecular mechanisms that lead to CFTR dysfunction has stimulated the design of therapeutic strategies aimed at restoration of CFTR function. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This thesis focuses on existing knowledge about CF with emphasis on the basic defect of the disease and the current standard of care. Recent and noteworthy papers were collected and synthesized. Current treatments were examined for specificity and success in reducing symptoms.