Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies

• Main Authors: Fahad A. Almughem, Ahmad M. Aldossary, Essam A. Tawfik, Mohammad N. Alomary, Waleed S. Alharbi, Mohammad Y. Alshahrani, Abdullah A. Alshehri
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Pharmaceutics
• Subjects: cystic fibrosis; cystic fibrosis transmembrane conductance regulator (CFTR) gene; gene editing; nanocarriers
• Online Access: https://www.mdpi.com/1999-4923/12/7/616

Cystic Fibrosis (CF), an autosomal recessive genetic disease, is caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). This mutation reduces the release of chloride ions (Cl⁻) in epithelial tissues, and hyperactivates the epithelial sodium channels (ENaC) which aid in the absorption of sodium ions (Na⁺). Consequently, the mucus becomes dehydrated and thickened, making it a suitable medium for microbial growth. CF causes several chronic lung complications like thickened mucus, bacterial infection and inflammation, progressive loss of lung function, and ultimately, death. Until recently, the standard of clinical care in CF treatment had focused on preventing and treating the disease complications. In this review, we have summarized the current knowledge on CF pathogenesis and provided an outlook on the current therapeutic approaches relevant to CF (i.e., CFTR modulators and ENaC inhibitors). The enormous potential in targeting bacterial biofilms using antibiofilm peptides, and the innovative therapeutic strategies in using the CRISPR/Cas approach as a gene-editing tool to repair the CFTR mutation have been reviewed. Finally, we have discussed the wide range of drug delivery systems available, particularly non-viral vectors, and the optimal properties of nanocarriers which are essential for successful drug delivery to the lungs.