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  or homozygous for the common class II mutation Phe508del. 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  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, a comprehensive description of the treatment adjustment period has not been previously reported, here we provide a detailed account of this phenomenon.
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.