Curative Measures for Cystic Fibrosis: A Perspective on Current Stem Cell–Based, Gene, and Small Molecule Therapies

Abstract

Cystic fibrosis (CF), which is caused by a defect or deficiency in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, continues to be a life-limiting multiorgan disease with severe phenotypic manifestations in affected patients. Current approaches to CF therapy have advanced far beyond symptomatic treatment, targeting the aberrant CFTR for therapeutic results. Novel small molecule treatments, or CF modulators, were the first to significantly improve the quality of life for patients with CF. These low-molecular-weight drugs can easily traverse the cell membrane and effect transcriptive changes in cells, albeit only for those with the specific mutations addressed by the drugs. However, other stem cell–based treatments, such as mesenchymal stromal cell therapy or induced pluripotent stem cell therapy, and gene therapies, such as CRISPR/Cas9 and viral vectors, are being researched as potential mutation-independent cures. These therapies have yet to progress to clinical trials, but their efficacies in various CF models prove their promise as future treatment options and potential cures. In this review, 3 potential contemporary therapies for CF and their current statuses and trajectories as clinical tools are discussed.