Human nasal epithelial organoids as a non-invasive, personalized model for predicting effectiveness of CFTR modulators in cystic fibrosis patients

Period of Performance: 07/24/2017 - 06/30/2018


Phase 2 SBIR

Recipient Firm

Path Bioanalytics, Inc.
Principal Investigator


Project Summary The discovery of the single gene (CFTR) responsible for cystic fibrosis (CF) has been transformational in focusing treatment efforts on the development and approval of drugs that restore the function of the CFTR protein. Excellent clinical response for CF patients with ?gating? mutations is observed following treatment with the CFTR modulator drug ivacaftor (VX-770); however, for the remaining ~95% of patients, no effective treatments exist. More than two thousand different CFTR mutations, combined with other genetic and environmental factors, result in significant variability in response among individuals to a single therapy. To improve the clinical outcome for all CF patients, it is important that patient-specific in vivo features of CF are faithfully reproduced in vitro for predictive screening assays. To meet that need we have developed a novel organoid-based screening platform, Sphera?, using cells derived from a patient?s nasal epithelia. Sphera couples patient-specific organoids with an integrated assessment of CFTR function, including organoid morphology and viscoelastic characterization of luminal mucus using our proprietary microrheology analytics. In Phase I we developed the Sphera platform and validated its utility in measuring organoid response to CFTR rescue. During Phase II we will define the efficiency and sensitivity of the Sphera platform and scale it for high throughput use in a cross-sectional clinical study. A multi-disciplinary, industry-academic partnership with expertise in all areas essential to the successful accomplishment of these aims has been assembled, including investigators with expertise in microfluidics, advanced mathematics, CF lung physiology, and clinical studies. Sphera will be commercialized as a full service platform marketed to clinical and drug development clients. The primary endpoint of this work is to develop a novel tool with dual utility in both CFTR modulator development and precision treatment for individuals with CF.