Patient-Derived Intestinal Organoids in the Global Cystic Fibrosis Landscape

Area of Science:

• Biomedical Science
• Genetics
• Global Health

Background:

• Cystic fibrosis (CF) diagnosis and care are significantly limited in low- and middle-income countries (LMICs).
• Barriers include restricted newborn screening, limited diagnostic testing, underrepresentation of diverse CFTR variants, and inadequate access to basic therapies.
• Sparse patient registries hinder epidemiological understanding and resource allocation in LMICs.

Purpose of the Study:

• To explore the potential of patient-derived intestinal organoids (PDIOs) in addressing diagnostic and therapeutic gaps in CF care within LMICs.
• To evaluate PDIOs as a platform for functional diagnosis, genotype-phenotype correlation, and drug testing, particularly for rare CFTR variants.
• To identify strategies for implementing PDIO technology in LMICs to mitigate global health disparities in CF.

Main Methods:

• Utilizing patient-derived intestinal organoids (PDIOs) for functional CFTR analysis.
• Characterizing genotype-phenotype correlations using PDIO models.
• Assessing the feasibility of comprehensive CFTR sequencing and drug screening with PDIOs, including for rare variants.

Main Results:

• PDIOs provide a versatile platform for functional diagnosis and characterization of CF, including rare CFTR variants.
• PDIOs can generate renewable material for advanced genetic analysis and drug testing.
• Implementation challenges in LMICs exist but can be addressed through mentorship, collaboration, and funding.

Conclusions:

• Patient-derived intestinal organoids (PDIOs) offer a promising approach to improve CF diagnosis and care in resource-limited settings.
• Integrating PDIOs can help bridge global disparities in CF treatment by enabling personalized medicine and addressing variant-specific challenges.
• Successful implementation requires coordinated scientific, clinical, and policy efforts to overcome cost and access barriers.