TY - JOUR T1 - Personalised CFTR Pharmacotherapeutic Response Testing and Therapy of Cystic Fibrosis JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02457-2017 SP - 1702457 AU - Cormac McCarthy AU - John J. Brewington AU - Beth Harkness AU - John P. Clancy AU - Bruce C. Trapnell Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/03/15/13993003.02457-2017.abstract N2 - Cystic fibrosis (CF) is a fatal, multisystem, genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride transporter critical to luminal fluid homeostasis at respiratory airway and other ductal epithelial surfaces. Therapeutic options for some CF patients were transformed by the approval of ivacaftor and lumacaftor/ivacaftor, which are indicated, respectively, for patients heterozygous for a subset of rare class III mutations [1] or homozygous for the common class II mutation Phe508del.[2] Notwithstanding, more than 40% of CF patients do not meet the CFTR mutation-specific inclusion criteria and are excluded from these therapies, and while it is impractical to conduct a clinical trial for each new pharmacotherapy-responsive CFTR mutation identified, an evolution of the drug approval process now permits drug label expansion based on in vitro physiological response testing. Indeed, the development of novel patient cell-based methods such as cultured intestinal organoids [3, 4] or nasal epithelial spheroids [5] permit in vitro testing of targeted CFTR molecular therapies. Here, we report the use of a novel preclinical test in one such patient to demonstrate patient-specific functional correction of CFTR ex vivo followed by initiation of therapy and functional correction in vivo. Further, while adverse respiratory effects have been reported with lumacaftor/ivacaftor therapy,[6] a comprehensive description of the treatment adjustment period has not been previously reported, here we provide a detailed account of this phenomenon.Pharmacotherapeutic response testing identified CFTR Ser1159Pro as responsive to cystic fibrosis modulator therapyFootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. McCarthy has nothing to disclose.Conflict of interest: Dr. Brewington has nothing to disclose.Conflict of interest: Ms. Harkness has nothing to disclose.Conflict of interest: Dr. Clancy has nothing to disclose.Conflict of interest: Dr. Trapnell has nothing to disclose. ER -