Drug helps to partially reverse cystic fibrosis genetic defect

American researchers have successfully treated cystic fibrosis patients with a new drug targeting the cause of the disease. Patients carrying a common genetic mutation associated with cystic fibrosis were treated with the drug VX-770. The drug improved their condition by increasing the activity of the chloride ion channel, cystic fibrosis transmembrane conductance regulator (CFTR), which is disrupted in the disease.

'There has never been such a sense of hope and optimism in the cystic fibrosis community. This is the first time there's been a treatment for the basic defect in cystic fibrosis. If we can treat it early, maybe we won't have all the infections that destroy the lungs and eventually takes people's lives away', said Dr Robert Beall, president of the American Cystic Fibrosis Foundation.

Cystic fibrosis is caused by mutations in the CFTR gene, which encodes the CFTR chloride ion channel. Defective CFTR ion channels leads to inadequate transport of chloride ions in the lungs. This causes excess accumulation of thick, sticky, mucus within the lungs, making the body more prone to infections. In the UK over 8,500 children and young adults are affected by cystic fibrosis.

Several different mutations in the CFTR gene can lead to cystic fibrosis. The most common mutation, delta F508, results in severe changes in the structure of the CFTR ion channel. These changes are so severe that the protein is not transported to its site of action at the cells surface. Another common mutation, G551D-CFTR, allows the protein to correctly localise at the cell surface, however it is unable to efficiently transport chloride ions. It is this mutation that was present in the patients selected for the drug trial.

The drug trial assessed the safety of VX-770 and found that its adverse effects were within acceptable limits. The study also examined the functionality of the CFTR ion channel and the lung function of 39 cystic fibrosis patients treated with the drug. Dose-dependent improvements were observed in both CFTR ion channel function and lung function.

'The effects of VX-770 on CFTR-mediated ion transport and lung function suggest that the improvement of CFTR function may be a viable therapeutic approach in cystic fibrosis', write the authors of the study led by Dr Frank Accurso of the University of Colorado.

'Therapies for cystic fibrosis have been limited to alleviating clinical manifestations…This research represents a milestone along the pathway of discovery leading to better preventions, treatments, and cures', writes Dr Michael Welsh, Professor of Medicine at the University of Iowa, who was not involved in the study.

Further studies with larger numbers of patients and for longer durations are required, before VX-770 can be established as a safe and effective drug in the treatment of cystic fibrosis.

This study was published in the New England Journal of Medicine.