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.

Public Health Relevance

Individuals with cystic fibrosis face two realities: the extreme diversity in known CFTR mutations and the unpredictable response of CFTR modulator therapies in individual patients. This project expands the development of a comprehensive screening platform to rapidly identify the most promising therapy for individuals with cystic fibrosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44HL130189-03
Application #
9533194
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Sheridan, John T
Project Start
2016-01-12
Project End
2019-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Path Bioanalytics, Inc.
Department
Type
DUNS #
079370190
City
Chapel Hill
State
NC
Country
United States
Zip Code
27514