• John Paul Clancy, Calvin U Cotton, Scott H Donaldson, George M Solomon, Donald R VanDevanter, Michael P Boyle, Martina Gentzsch, Jerry A Nick, Beate Illek, John C Wallenburg, Eric J Sorscher, Margarida D Amaral, Jeffrey M Beekman, Anjaparavanda P Naren, Bridges Robert J RJ Chicago Medical School, United States., Philip J Thomas, Garry Cutting, Steven Rowe, Anthony G Durmowicz, Martin Mense, Kris D Boeck, William Skach, Christopher Penland, Elizabeth Joseloff, Hermann Bihler, John Mahoney, Drucy Borowitz, and Katherine L Tuggle.
• Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States. Electronic address: john.clancy@cchmc.org.
• J. Cyst. Fibros. 2019 Jan 1; 18 (1): 22-34.

BackgroundNew drugs that improve the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein with discreet disease-causing variants have been successfully developed for cystic fibrosis (CF) patients. Preclinical model systems have played a critical role in this process, and have the potential to inform researchers and CF healthcare providers regarding the nature of defects in rare CFTR variants, and to potentially support use of modulator therapies in new populations.MethodsThe Cystic Fibrosis Foundation (CFF) assembled a workshop of international experts to discuss the use of preclinical model systems to examine the nature of CF-causing variants in CFTR and the role of in vitro CFTR modulator testing to inform in vivo modulator use. The theme of the workshop was centered on CFTR theratyping, a term that encompasses the use of CFTR modulators to define defects in CFTR in vitro, with application to both common and rare CFTR variants.ResultsSeveral preclinical model systems were identified in various stages of maturity, ranging from the expression of CFTR variant cDNA in stable cell lines to examination of cells derived from CF patients, including the gastrointestinal tract, the respiratory tree, and the blood. Common themes included the ongoing need for standardization, validation, and defining the predictive capacity of data derived from model systems to estimate clinical outcomes from modulator-treated CF patients.ConclusionsCFTR modulator theratyping is a novel and rapidly evolving field that has the potential to identify rare CFTR variants that are responsive to approved drugs or drugs in development.Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

11 keywords...

hide…