Patient-Derived Intestinal Organoids in the Global Cystic Fibrosis Landscape

Abstract

Cystic fibrosis (CF) care has advanced rapidly, yet diagnosis and inclusion in patient registries remain severely limited in low- and middle-income countries (LMICs). Barriers include restricted newborn screening, limited availability of sweat chloride testing, and underrepresentation of non-European CFTR variants in standard panels. Sparse registries further impede epidemiological insight and resource planning. Also, access to comprehensive CF care remains a major challenge in LMICs, where limitations in basic therapies, including pancreatic enzyme replacement, airway clearance strategies, and infection control, continue to result in markedly reduced life expectancy. Within this context, access to CFTR modulators (CFTRm) represents an additional and critical barrier, constrained by prohibitive costs, restricted variant eligibility, and few tiered pricing mechanisms. Patient-derived intestinal organoids (PDIOs) offer a versatile platform to help address some of these gaps. PDIOs enable functional diagnosis, genotype-phenotype characterization, and renewable material for comprehensive CFTR sequencing and drug testing, including for rare variants. While implementation in LMICs is challenging, targeted mentorship, collaborative screening pipelines, and sustained funding could expand access. Integrating PDIOs into CF care could help bridge some global disparities, but success will require coordinated scientific, clinical, and policy efforts.