Cystic Fibrosis Gene Therapy Causes Modest Improvements

Patients with Cystic Fibrosis (CF) have a mutation in a gene that encodes a chloride pump. Without a functional chloride pump, the production of mucus by the ductal systems of the lungs and other organs produce a very thick, difficult to move mucus that tends to clog the lungs and cause suffocation. In order to live, CF patients have to take a battery of pills every day just to keep the symptoms at bay. Gene therapy could be a simpler and more effective treatment. Several clinical trials have examined the use of various gene therapy vectors to treat CF patients, but these trials have not been overly successful.

It seems that gene therapy engineers some cells with the normal copy of the CF gene, but these cells are soon sloughed off and do little good. Therefore, a new paradigm is to repeatedly administer the gene vector. This new strategy has stabilized and slightly improved lung function in a clinical trial that tested 136 cystic fibrosis patients. Patients who received the gene therapy showed no decline of lung function, but instead had a 3% improvement on average, after taking the gene therapy once a month for a year. Patients who received the placebo showed a decline of 3-4% on average over the same period. These results were published in Lancet Respiratory Medicine.

This is the first evidence worldwide which shows that if you give gene therapy to CF patients it has a protective effect.

Prof Eric Alton, of Imperial College London, who led the trial, warned: “The effect is modest and it is variable. It is not ready to go straight into the clinic yet.”

Prof Alton and his colleagues at the UK Cystic Fibrosis Gene Therapy consortium includes scientists at Edinburgh and Oxford Universities as well as Imperial College. They hope to have a further trial next year.

Cystic fibrosis leads to a buildup of thick, sticky mucus that causes debilitating infections in the nose, throat and lungs. Patients’ average life expectancy is 41.

Trial participant Kieran Kelly usually takes about 40 pills, injections and inhaled medicines throughout the day. Mr. Kelly told BBC News: “I did feel a lot healthier. It might have been psychological, but I did feel better in myself. You have to live every day that you have,” he added. “You have to be as positive as you can, just live your life and enjoy it.”

Mr. Kelly’s fiancé, Nadia Lloyd, said: “You have to be quite hopeful. When we first met [nine years ago], the average life expectancy was 28. So every time you see medical developments, it is always so encouraging”.
Unfortunately, the two of them know the new gene therapy probably will not be ready in time to help Mr. Kelly. “The chances are that it will have an effect on anyone taking part in the trials are quite slim,” he said. It would be great if it does.” However Miss Lloyd said that Mr. Kelly has already benefited from drugs developed as a result of other people taking part in previous trials. She added: “What Kieran is doing could help so many people in the future. I am very proud of him.”

Prof Stuart Elborn, of Queen’s University in Belfast, said the results were “encouraging” but the therapy had been no more effective than some of the drugs currently available. He called for more small-scale tests to see if a larger dose would be more effective. “If I was on the board of a pharmaceutical company, I would require further studies to determine the best dose and whether the current treatment could be combined with other drugs to increase the effect,” he said. “It is too soon to proceed with larger phase-three trials costing many millions.”

Cystic Fibrosis Trust chief executive Ed Owen said: “The advantage of gene therapy is that it attacks the basic defect of cystic fibrosis and that has the potential to reduce the daily routine of drugs that those with cystic fibrosis endure each day and (offers the possibility) of long-term improvement to transform their lives”.