title: Therapeutics development for cystic fibrosis: a successful model for a multisystem genetic disease.
abstract: Cystic fibrosis (CF) is a progressive genetic disease primarily involving the respiratory and gastrointestinal tracts. Multiple therapies directed at CF symptoms and clinical management strategies have emerged from iterative cycles of therapeutics development, helping to change the face of CF from a fatal childhood affliction to a disease in which nearly 50% of U.S. patients are adults. However, as a consequence of therapeutic advances, the burden of CF care is high, and despite progress, most patients succumb to respiratory failure. Addressing the basic defect in CF with systemic small molecules is evolving as a promising approach. A successful collaboration between a voluntary health organization and a pharmaceutical company, complemented by academic investigators and patients, has led to the clinical development of investigational drugs that restore function to defective CFTR protein in various tissues in CF patients. Important activities, leverage points, and challenges in this exemplary collaboration are reviewed with hope that the CF and other genetic disease communities can benefit from the lessons learned in generating new therapeutic approaches in CF.
authors.affiliation: Cystic Fibrosis Foundation Therapeutics, Inc., Bethesda, Maryland 20814, USA. melissaashlock@gmail.com
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Ashlock
authors.forename: Eric R
authors.initials: ER
authors.lastname: Olson
mesh_terms: D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000502:physiology; D055808:Drug Discovery / Q000379:methods*; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008297:Male; D009154:Mutation; D010654:Phenylbutyrates / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000209:etiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology / Q000401:mortality; D012307:Risk Factors
chemical_list: D015507:Drugs, Investigational; D010654:Phenylbutyrates; D047428:Protein Kinase Inhibitors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019833:Genistein