Current and novel therapeutic strategies for the management of cystic fibrosis

ABSTRACT

Introduction: Cystic fibrosis (CF), is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and affects thousands of people throughout the world. Lung disease is the leading cause of death in CF patients. Despite the advances in treatments, the management of CF mainly targets symptoms. Recent CFTR modulators however target common mutations in patients, alleviating symptoms of CF. Unfortunately, there is still no approved treatments for patients with rare mutations to date.

Areas covered: This paper reviews current treatments of CF that mitigate symptoms and target genetic defects. The use of gene and drug delivery systems such as viral or non-viral vectors and nano-compounds to enhance CFTR expression and the activity of antimicrobials against chronic pulmonary infections respectively, will also be discussed.

Expert opinion: Nano-compounds tackle biological barriers to drug delivery and revitalize antimicrobials, anti-inflammatory drugs and even genes delivery to CF patients. Gene therapy and gene editing are of particular interest because they have the potential to directly target genetic defects. Nanoparticles should be formulated to more specifically target epithelial cells, and biofilms. Finally, the development of more potent gene vectors to increase the duration of gene expression and reduce inflammation is a promising strategy to eventually cure CF.

KEYWORDS:

• Antimicrobials
• cftr modulators
• cystic fibrosis
• gene therapy
• management
• nano-compounds

Article highlights

• Cystic fibrosis is the result of mutations in the CFTR gene

• CF is a multisystemic disease with pulmonary afflictions being the main cause of death in patients

• Management of the disease is achieved by alleviating the symptoms, notably with mucolytics agents, bronchodilators, anti-inflammatory drugs, antibiotics, respiratory techniques, and organ transplantation when necessary

• Nanocarrier drug delivery systems improve current therapies by enhancing drug and gene delivery, while also reducing associated toxicity

• CFTR modulators are a new option to directly target specific genetic defects observed in some patients

• Gene therapy and gene editing with CRISPR-nucleases present the opportunity to correct faulty CFTR gene, possibly recover protein function and cure CF

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.