title: Lumacaftor/ivacaftor combination for cystic fibrosis patients homozygous for Phe508del-CFTR.
abstract: Cystic fibrosis (CF) is a life-shortening inherited disease caused by the loss or dysfunction of the CF transmembrane conductance regulator (CFTR) channel activity resulting from mutations in the CFTR gene. Phe508del is the most prevalent mutation, with approximately 90% of all CF patients carrying it on at least one allele. Over the past two or three decades, significant progress has been made in understanding the pathogenesis of CF, and in the development of effective CF therapies. The approval of Orkambi® (lumacaftor/ivacaftor) marks another milestone in CF therapeutics development, which, with the advent of personalized medicine, could potentially revolutionize CF care and management. This article reviews the rationale, progress and future direction in the development of lumacaftor/ivacaftor combination to treat CF patients homozygous for the Phe508del-CFTR mutation.
authors.affiliation: Department of Pediatrics, Physiology, University of Tennessee Health Science Center, and University of Tennessee Cystic Fibrosis Care and Research Center at Le Bonheur Children's Hospital-Methodist University Hospital, Memphis, Tennessee, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, and University of Tennessee Cystic Fibrosis Care and Research Center at Le Bonheur Children's Hospital-Methodist University Hospital, Memphis, Tennessee, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, and University of Tennessee Cystic Fibrosis Care and Research Center at Le Bonheur Children's Hospital-Methodist University Hospital, Memphis, Tennessee, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Strokes
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. anaren@cchmc.org.
authors.forename: A P
authors.initials: AP
authors.lastname: Naren
mesh_terms: D000627:Aminophenols / Q000008:administration & dosage*; D000631:Aminopyridines / Q000008:administration & dosage*; D052117:Benzodioxoles / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004359:Drug Therapy, Combination; D006801:Humans; D009154:Mutation; D057285:Precision Medicine; D015363:Quinolones / Q000008:administration & dosage*
chemical_list: D000627:Aminophenols; D000631:Aminopyridines; D052117:Benzodioxoles; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; C569105:lumacaftor
keywords: CFTR; Cystic fibrosis; Lumacaftor/ivacaftor; Orkambi®; Phe508del