Targeted Therapy for Restoring CFTR Activity: From Experimental to Clinical Features

Area of Science:

• Genetics and Molecular Biology
• Pharmacology
• Personalized Medicine

Background:

• Cystic fibrosis (CF) is a common rare genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
• Over 2200 CFTR variants necessitate detailed functional characterization for targeted therapies.
• Traditional CF treatments focus on symptom management, but new molecular therapies are emerging.

Purpose of the Study:

• To review strategies for restoring CFTR functional defects based on specific CFTR variants.
• To discuss the application of experimental and clinical drugs for CF treatment.
• To provide an overview of the current state of theratyping for CF drug testing.

Main Methods:

• Review of scientific literature on CFTR gene variants and therapeutic strategies.
• Analysis of small molecule drugs targeting CFTR channel defects.
• Evaluation of patient-specific cellular models for drug response testing (theratyping).

Main Results:

• Development of small molecules targeting CFTR defects represents a significant therapeutic advance.
• Patient-specific cellular models enable personalized treatment evaluation and therapeutic advances.
• Integrated precision diagnostics and therapy at molecular, cellular, and clinical levels show potential to alter CF's natural history.

Conclusions:

• Restoring CFTR function through targeted therapies and personalized approaches offers improved quality of life and life expectancy for CF patients.
• Theratyping using patient-derived cells is crucial for evaluating drug efficacy and guiding personalized CF treatment.
• A comprehensive understanding of CFTR variants and their functional impact is essential for advancing precision medicine in CF care.