Work

CFTR rescue in W1282X cystic fibrosis patient-derived intestinal organoids (PDIOs) mediated by translational readthrough-inducing drugs (TRIDs)

Year: 2025

Type: article

Abstract: Purpose: variants, including nonsense variants, often lack access to these therapies. Nonsense variants lead to nonfunctional CFTR proteins and contribute to more severe CF symptoms. Research efforts focus on understanding the effects of these variants on disease severity and response to treatment. Methods: This study utilizes patient-derived intestinal organoids to evaluate the recovery of CFTR function in cells with nonsense variants. Results: Specifically, we tested 3 translational readthrough-inducing molecules: NV848, NV914, and NV930. Our studies highlighted the positive effect of NV848 on patient organoid swelling, improving CFTR channel function, whereas NV914 and NV930 did not induce organoid swelling, similar to PTC124 treatment. Conclusion: variants, addressing a critical unmet need in cystic fibrosis treatment.

Source: Genetics in Medicine Open

DOI: 10.1016/j.gimo.2025.103472