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

Project SummaryThe discovery of the single geneCFTRresponsible for cystic fibrosisCFhas been transformational in focusing treatment efforts on the development and approval of drugs that restore the function of the CFTR proteinExcellent clinical response for CF patients withgatingmutations is observed following treatment with the CFTR modulator drug ivacaftorVXhoweverfor the remainingof patientsno effective treatments existMore than two thousand different CFTR mutationscombined with other genetic and environmental factorsresult in significant variability in response among individuals to a single therapyTo improve the clinical outcome for all CF patientsit is important that patient specific in vivo features of CF are faithfully reproduced in vitro for predictive screening assaysTo meet that need we have developed a novel organoid based screening platformSpherausing cells derived from a patient s nasal epitheliaSphera couples patient specific organoids with an integrated assessment of CFTR functionincluding organoid morphology and viscoelastic characterization of luminal mucus using our proprietary microrheology analyticsIn Phase I we developed the Sphera platform and validated its utility in measuring organoid response to CFTR rescueDuring 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 studyA multi disciplinaryindustry academic partnership with expertise in all areas essential to the successful accomplishment of these aims has been assembledincluding investigators with expertise in microfluidicsadvanced mathematicsCF lung physiologyand clinical studiesSphera will be commercialized as a full service platform marketed to clinical and drug development clientsThe 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