Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease

• Published in: Cochrane database of systematic reviews 2013-11 (11), p.CD005599-CD005599
• Main Authors: Lee, Tim W R, Southern, Kevin W
• Format: Article
• Language: English
• Subjects: Cystic Fibrosis - genetics; Cystic Fibrosis - therapy; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - therapeutic use; Gene Transfer Techniques; Genetic Therapy - adverse effects; Genetic Therapy - methods; Humans; Randomized Controlled Trials as Topic; Respiratory Function Tests; Targeted Gene Repair - adverse effects; Targeted Gene Repair - methods
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD005599.pub4

Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 22 August 2013.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2013.Date of most recent search: 04 September 2013. Randomised controlled trials comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. Three randomised controlled trials met the inclusion criteria for this review, involving a total of 155 participants. Fourteen studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis.Although the first Moss study reported a significant improvement in respiratory function (forced expiratory volume at one second) 30 days after participants had received their first dose of gene therapy agent, this finding was not confirmed in their larger second study or in our meta-analysis.In participants who received the CFTR gene transfer agents in the Alton study, "influenza-like" symptoms were found (risk ratio 7.00 (95% confidence interval 1.10 to 44.61)). There were no other significant increases in adverse events in any of the studies.Alton measured ion transport in the lower airways and demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% confidence interval 3.77 to 9.95). In these participants th