No gene therapy so far had ever resulted in breakthrough, failing to demonstrate any long-term clinical improvement.

A recent research published in the journal The Lancet Respiratory Medicine has, for the first time, shown that gene therapy can be a significantly promising treatment for cystic fibrosis.

Researchers have been successful in replacing the defective gene with a working copy via inhalable molecules of DNA that deliver the gene to lung cells.

This study was funded by the UK Medical Research Council (MRC), in partnership with the National Institute for Health Research (NIHR).

Cystic Fibrosis

Cystic fibrosis is a rare genetic disorder. One out of every 2,500 newborns is diagnosed with cystic fibrosis in the UK, with 90,000 people affected worldwide. It manifests due to mutations in a single gene known as the cystic fibrosis transmembrane conductance regulator (CFTR). This mutation causes the lining of the lungs to secrete abnormally thick mucus, which leads to recurrent adverse lung infections. The latter ultimately result in severe lung damage that is often the cause of death – 90% of deaths are attributed to this factor.

To date, scientists have uncovered about 2000 CFTR mutations.

Efforts Of The Research Team

Since the discovery the cystic fibrosis had a genetic basis (1989), researchers have developed various viral and non-viral vector systems for the delivery of a working copy of the CFTR gene into the lung cells. However, no gene therapy so far had ever resulted in a breakthrough, failing to demonstrate any long-term clinical improvement.

Under the coordination of the UK Cystic Fibrosis Gene Therapy Consortium, the two-year study trial consisted of 136 patients of cystic fibrosis from the UK, aged 12 years and above. The patients were randomly assigned to the gene therapy group (receiving 5ml of inhalable pGM169/GL67A) or placebo group (receiving saline). Both, the intervention and the placebo, were administered at monthly intervals over a period of one year.

At the end of the randomized control trial, lung function was evaluated via the general clinical method of recording volume of air forcibly exhaled in a second (FEV1).

Promising Results For First Time

After one year, clinical evaluation revealed that the FEV1 of 62 patients who had received the therapy was 3.7 percent greater than those on placebo*. This indicates stabilization and maintenance of respiratory function. There was some amount of inconsistency, with some patients showing better clinical results than others. Most significantly, half of the patients who had the worst lung infections had a FEV1 of 6.4 percent – double of that reported at the start of treatment.

On the whole, the gene therapy was well tolerated by the patients. Both groups, the intervention and placebo, demonstrated similar rates of adverse episodes.

Hopes For Future

“Patients who received the gene therapy showed significant, if modest, benefits in tests of lung function as compared to the placebo group. There were no safety concerns reported either,” said senior author Professor Eric Alton from the National Heart and Lung Institute at Imperial College London. “Even though the effect of the therapy was inconsistent, the overall results are encouraging and beneficial.”

Senior co-author Professor Stephen Hyde from the Gene Medicine Research Group at the University of Oxford added that the research team was actively pursuing the idea of using non-viral gene therapy as well. They were conducting analysis using different dosage and combinations, and making use of more efficient transportation vectors.

Dr Alastair Innes from Western General Hospital, Edinburgh, UK, another senior co-author, said that the publication of this study is a breakthrough for those suffering from cystic fibrosis. The team thanked the patients who participated in the randomized control trial and appreciated their collaborative efforts with the research team.

*The 95% confidence interval for the effect size is 0.1% to 7.3%. Even though the best estimate of effect size is 3.7%, the data are consistent with the true effect size lying within the range 0.1% to 7.3%. This interval includes values from no effect to clear clinical relevance.