Gene therapy and drug studies show promise for treatment of cystic fibrosis

Scientists have used two new techniques to fix defects in lung cells from people with cystic fibrosis, raising hope for new treatments for the disease in the future. The first study, published in the journal Plos Biology, used a gene therapy technique to treat the cells, whilst the second study, published in the American Journal of Respiratory Cell and Molecular Biology, used a drug called miglustat.

Cystic fibrosis is an inherited genetic disorder that affects more than 8000 children and young adults in the UK. It affects individuals who carry two faulty copies of a gene called cystic fibrosis transmembrane regulator (CFTR), and results in mucus throughout the body becoming thicker and stickier than usual. This prevents several organs, in particular the lungs and digestive system, from functioning properly, and makes sufferers very susceptible to infections which can often be incurable or life-threatening. There are currently no cures or treatments that target the cause of the disease, although symptoms can be alleviated.

In the first study, researchers at the University of North Carolina at Chapel Hill School of Medicine used a genetically-engineered parainfluenza virus (which is one of the viruses that causes common colds) to deliver normal, fully functional CFTR genes to lung cells from individuals with cystic fibrosis that were being grown in a dish to create a model of airway tissue. Using this technique, the researchers were able to correct the CFTR gene in 60 to 70 per cent of cells, and these cells produced normal mucus secretions. Importantly, they found that they only needed to deliver the corrected CFTR gene to 25 per cent of cells for normal function to be restored to the model airway tissue.

Professor Ray Pickles, who led the study, said: 'we discovered that if you take a virus that has evolved to infect the human airways, and you engineer a normal CFTR gene into it, you can use this virus to correct all of the hallmark cystic fibrosis features in the model system that we used'. The technique could not yet be used in humans, as the virus delivery system would first need to be rigorously tested for safety, but hope remains for the future.

In the second study, researchers at the Université de Poitiers, France, treated lung cells carrying mutations in the CTFR gene with low doses of miglustat, a drug currently approved for the treatment of rare metabolic disorders. They found that after three to four days, CFTR activity was restored to normal, and could be maintained thereafter. The results of this study have prompted the drug's manufacturer, Actelion Pharmaceuticals, Switzerland, to perform further investigations and to reconsider their earlier decision to halt clinical trials for the use of miglustat to treat cystic fibrosis sufferers.