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Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung diseaseLee TWR, Southern KW
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SummaryReplacing the defective gene is a potential treatment for progressive lung disease in people with cystic fibrosisIn cystic fibrosis (CF) the gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR) is faulty. People with CF suffer from progressive lung infection. This lung damage reduces life expectancy. CFTR gene transfer agents may be an effective treatment as they deliver a correct copy of the CFTR gene to lung cells. We found three trials with 155 participants to include in this review. The trials compare gene therapy to placebo nebulised to the lungs. The trials were of different designs and used different agents. This meant we could not combine them all in a meta-analysis. We found significant changes toward normal ion transport values in the lower airways of people who received gene transfer agents. However, we found no evidence that outcome measures which are clinically relevant to people with CF had improved. In one study "influenza-like" symptoms were significantly more common in people who received CFTR gene transfer agents. We conclude that at the moment there is no evidence to support the use of CFTR gene transfer agents as a treatment for lung disease in people with CF. We recommend that future studies are designed and reported clearly so that their results can be incorporated into a systematic review.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2010 Issue 1, Copyright © 2010 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
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April 18. 2007 AbstractBackgroundCystic 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. ObjectivesTo 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. Search strategyWe 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: 26th August 2009. Selection criteriaRandomised 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. Data collection and analysisThe 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. Main resultsThree randomised controlled trials met the inclusion criteria for this review, involving a total of 155 participants. Thirteen 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 (FEV1) 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 (CI) 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% CI of 3.77 to 9.95). In these participants there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. Authors' conclusionsThere is currently no evidence to support the use of CFTR gene transfer reagents as a treatment for lung disease in people with cystic fibrosis. Future studies need to investigate clinically important outcome measures. |