Journal Article Review Epublish
PubMed: 42654157 DOI: 10.3390/pharmaceutics18081040
Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research.
Pharmaceutics 18(8)
Authors: Xavier Buin, Rosy Ghanem, Ines Pankonien, Frédéric Becq, Margarida Amaral, Tristan Montier
Affiliations
- UnivBrest, Inserm, EFS, UMR 1078, GGB, F-29200 Brest, France.
- Service de Génétique Médicale et de Biologie de la Reproduction, CHU de Brest, F-29200 Brest, France.
- BioISI-Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, Campo Grande, C8 bdg, 1749-016 Lisboa, Portugal.
- Laboratoire PRéTI, University of Poitiers, F-86022 Poitiers, France.
Abstract
Since the development of the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator in 2012, these therapies have revolutionized patients' health. They are now the most effective treatment for people with cystic fibrosis (pwCF). In fact, elexacaftor/tezacaftor/ivacaftor and vanzacaftor/tezacaftor/deutivacaftor, the latest combination therapies consisting of a CFTR potentiator and two CFTR correctors, improved lung function by 14% in pwCF. Other modulator therapies targeting CFTR mRNA and/or protein are currently under preclinical/clinical investigation. However, due to the variant-specific nature of these therapies, about 10% of pwCF in Europe remains without effective treatment, and many treated pwCF experience various adverse events such as headaches, infections, hepatotoxicity, hypertension, and depression. Therefore, mutation-agnostic strategies such as gene therapy are needed. They could expand treatment eligibility for all pwCF and improve outcomes. In fact, nucleic acid delivery (e.g., pDNA, mRNA, oligonucleotides, genome editing) or targeting non-CFTR channels to restore ion transport represent promising future additional directions for CF therapy. This review aims to discuss a potential combination between gene therapy approaches and existing modulators to improve treatment eligibility, safety, and efficacy.
MeSH
Genes, Fibrosis, Cystic Fibrosis, Nucleic Acids, Research, Therapeutics