title: Strategies in early clinical development for the treatment of basic defects of cystic fibrosis.
abstract: BACKGROUND
  Twenty-six years after the identification of the gene responsible for cystic fibrosis (CF), controversies still surround the pathogenesis of the disease that continues to burden and shorten lives. Therefore, finding effective therapeutic strategies that target the basic defect of CF is crucially needed.
  
  
  METHODS
  This review offers a comprehensive survey of fundamental therapies in early stages of development for the treatment of CF. The first part describes recent strategies targeting the basic defect either at the gene or at the transcript level. The second part summarizes a panel of novel strategies targeting protein repair. The third part reports strategies targeting non-CFTR channels.
  
  
  CONCLUSIONS
  Recent major breakthroughs in CF therapy have been made, raising hope to find a cure for CF. Apart from Vertex corrector and potentiator molecules (lumacaftor, ivacaftor, VX-661) and from ataluren, used to correct nonsense mutations, most compounds being currently tested are in very early (I-II) phases of development and definitive clinical results are keenly expected. Among the broad list of molecules and strategies being tested, the QR-010 compound and inhibitors of phosphodiesterase type 5 (sildenafil, vardenafil) could reveal a strong potentiality as therapeutic candidates to cure CF.
authors.affiliation: a Louvain centre for Toxicology and Applied Pharmacology , Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain , Brussels , Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dhooghe
authors.affiliation: a Louvain centre for Toxicology and Applied Pharmacology , Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain , Brussels , Belgium.
authors.forename: Jérémy Boris
authors.initials: JB
authors.lastname: Haaf
authors.affiliation: a Louvain centre for Toxicology and Applied Pharmacology , Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain , Brussels , Belgium.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Noel
authors.affiliation: a Louvain centre for Toxicology and Applied Pharmacology , Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain , Brussels , Belgium.
authors.forename: Teresinha
authors.initials: T
authors.lastname: Leal
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D014158:Transcription, Genetic
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: CFTR; Cystic Fibrosis; clinical trials; correctors; gene therapy; mRNA repair; non-CFTR ion channels; pharmacotherapy; phosphodiesterase type 5 inhibitors; potentiators