The Efficacy and Safety of Cystic Fibrosis Gene Therapy Clinical Trials: A Systematic Review and Meta-Analysis

Abstract

Background
Gene therapy has been proposed as a treatment approach for cystic fibrosis by replacing the single
defective gene, cystic fibrosis transmembrane regulator (CFTR), through topical lung delivery. Relatively
few studies have addressed gene therapy for cystic fibrosis.
Objectives
Via referral to the published literature, this study aimed to identify any success of the gene therapy
approach for cystic fibrosis regarding experimental and routine clinical outcomes in different drug
development stages, and to determine any adverse effects noted.
Methodology
A search of the PubMed database (NCBI) for 1989–2020 was made using predefined selection criteria for
clinical trials on patients with cystic fibrosis receiving viral and non-viral lung delivery systems of the
CFTR gene. Several features in the reviewed studies were examined, including clinical phase (1–3),
sample size, delivery target cells/vector, and reported adverse effects. A quantitative estimate of treatment
intervention success was evaluated using a meta-analysis approach.
Results
A total of 20 studies with 549 patients were included in the review. The studies involved the delivery of the
defective gene to the lung, nasal mucosa, and sinuses, and were mainly phase 1–2, randomized controlled
trials; there were no phase three studies. The vector for gene transfer was liposome or viral. % predicted
FEV1 was statistically significant between intervention and control patients in two trials. Gene transfer was
detected to a higher degree in intervention patients than control; this outcome measure was assessed using
bronchoscopy assessment of vector-specific DNA and mRNA expression in lung and nasal mucosa. These
effects, however, were temporary. The safety of the gene therapy approach was confirmed.
Conclusion
Reportedly, the gene therapy approach is safe but has limited and temporary efficacy. Newer approaches
should thus be engineered to deliver the necessary genetic material with the desired, full-scale efficacy.