Comparison of preclinical drug efficacy in nasal and intestinal patient-derived models of cystic fibrosis.

In vitro patient-derived models, predicting the benefit of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, have the potential to find effective drugs for cystic fibrosis patients (pwCF) through a personalized CFTR pharmacotherapeutic approach. To date, human nasal epithelial (HNE) cells and human intestinal organoids (HIOs) represent the most utilized in vitro system in Cystic Fibrosis (CF) research, carrying a patient-specific genomic background. The first one is expected to represent key processes occurring in the airways, and the second to mimic the features of the gastrointestinal tract. Both are important target tissues and are utilized as sensitive and robust tools for the diagnosis of CF. In this review, we evaluated the efficacy of nasal and intestinal models in predicting similar therapeutic responses of CFTR variants to CFTR modulators and other treatments by conducting an analysis of the published data reporting responses in both cellular models derived from the same individuals. The data confirm a high concordance in CFTR rescue across the two models, supporting their use as equally reliable and complementary theranostic tools for assessing in vitro drug efficacy of highly efficient CFTR modulator therapies (HEMT).