{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Molinski SV"],"funding":["Cystic Fibrosis Canada","Hospital for Sick Children","Canadian Institutes of Health Research","CIHR"],"pagination":["1224-1243"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5582412"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(9)"],"pubmed_abstract":["The combination therapy of lumacaftor and ivacaftor (Orkambi<sup>®</sup>) is approved for patients bearing the major cystic fibrosis (CF) mutation: <i>ΔF508</i> It has been predicted that Orkambi<sup>®</sup> could treat patients with rarer mutations of similar \"theratype\"; however, a standardized approach confirming efficacy in these cohorts has not been reported. Here, we demonstrate that patients bearing the rare mutation: c.3700 A>G, causing protein misprocessing and altered channel function-similar to ΔF508-CFTR, are unlikely to yield a robust Orkambi<sup>®</sup> response. While <i>in silico</i> and biochemical studies confirmed that this mutation could be corrected and potentiated by lumacaftor and ivacaftor, respectively, this combination led to a minor <i>in vitro</i> response in pa"],"journal":["EMBO molecular medicine"],"pubmed_title":["Orkambi® and amplifier co-therapy improves function from a rare <i>CFTR</i> mutation in gene-edited cells and patient tissue."],"pmcid":["PMC5582412"],"funding_grant_id":["MOP‐130461","GPG‐102171","CIHR GPG‐102171","CIHR MOP‐130461","CIHR MOP‐97954","MOP‐97954"],"pubmed_authors":["Ratjen F","Pomes R","Di Paola M","Li E","Wellhauser L","Ahmadi S","Villella A","Laselva O","Ray PN","Bear CE","Ouyang H","Huan LJ","Gonska T","Eckford PD","Lee PS","Molinski SV","Ip W","Du K","Miller JP","Kulleperuma K","Moraes TJ"],"additional_accession":[]},"is_claimable":false,"name":"Orkambi® and amplifier co-therapy improves function from a rare <i>CFTR</i> mutation in gene-edited cells and patient tissue.","description":"The combination therapy of lumacaftor and ivacaftor (Orkambi<sup>®</sup>) is approved for patients bearing the major cystic fibrosis (CF) mutation: <i>ΔF508</i> It has been predicted that Orkambi<sup>®</sup> could treat patients with rarer mutations of similar \"theratype\"; however, a standardized approach confirming efficacy in these cohorts has not been reported. Here, we demonstrate that patients bearing the rare mutation: c.3700 A>G, causing protein misprocessing and altered channel function-similar to ΔF508-CFTR, are unlikely to yield a robust Orkambi<sup>®</sup> response. While <i>in silico</i> and biochemical studies confirmed that this mutation could be corrected and potentiated by lumacaftor and ivacaftor, respectively, this combination led to a minor <i>in vitro</i> response in pa","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Sep","modification":"2026-04-30T14:45:01.772Z","creation":"2019-03-27T02:55:19Z"},"accession":"S-EPMC5582412","cross_references":{"pubmed":["28667089"],"doi":["10.15252/emmm.201607137"]}}