UK trials for 'breakthrough' cystic fibrosis treatment

The biggest test undertaken of a gene therapy treatment for cystic fibrosis is about to start in the UK.

Results, expected by 2010, stand a real chance of transforming the lives of patients and families affected by the devastating disease.

If the treatment succeeds, it could offer new hope to chancellor Gordon Brown and his wife Sarah, whose four-month-old son James Fraser has been diagnosed with the genetic condition.

The massive £20 million project, almost entirely funded by charitable donations, will be conducted by pioneering scientists in London, Oxford and Edinburgh.

They hope to prove that corrective genes can be administered to cystic fibrosis (CF) sufferers via a spray inhaler.

A trial due to begin in 2008 will for the first time attempt to show clinical evidence that gene therapy can improve the condition of patients with the disease.

If it succeeds, a commercially available treatment could soon follow.

The scientists do not expect to provide a complete cure, but hope the treatment will be the first in the world to tackle the underlying cause of CF rather than focus on the symptoms.

Patients could have their condition improved to an extent that will hugely improve their quality of life.

An initial study beginning next Spring will test new measurements of lung function and disease that are needed before the launch of the patient trial.

A total of 200 patients are taking part in this preliminary investigation based at the Brompton Hospital in London and Western General Hospital in Edinburgh.

For the clinical trial, 100 patients over the age of 12 will be recruited, half of whom will be given the genuine therapy and half a "dummy" treatment.

Lead researcher Professor Eric Alton, from the Brompton Hospital and Imperial College London, said: "What makes this trial very novel is that we will for the first time be testing for clinical improvement.

"In other words, what's the level of inflammation in your lungs - has that reduced? The number of bacteria in your lungs - has that reduced? The picture on the CT scan of your lungs - has that improved in any way?

"I don't think we're going to make Concorde on our first go. It's not going to cure the disease, but we'll see if we can get the plane off the ground and fly it for 50 yards."

If the results are promising, the scientists expect to team up with one or more private partners willing to stand the cost of a worldwide trial involving many more patients. This could run into hundreds of millions of pounds.

Discussions are already under way with a number of candidate companies.

CF is caused by a single defective gene that prevents salt and water moving properly across cell membranes in the lungs.

As a result the airways fill up with sticky mucus, which acts as a breeding ground for bacteria. Mucus also blocks pancreatic ducts, making it difficult to digest food.

About one in 25 people unwittingly carry a defective copy of the gene. It only proves harmful if a child is unlucky enough to inherit two copies, one from each parent.

Around one in 2,000 babies are born with CF, and currently between 7,500 and 9,000 sufferers are living with the disease in the UK. They can expect to live no more than 31 years, and much of their life will be spent struggling to control the terrible symptoms, which can include liver failure and diabetes.

The new gene therapy technique being tested involves the use of a nebuliser which injects a fine spray into the airways.

Within the spray are tiny soap-like bubbles called liposomes containing the precious DNA used to correct the genetic defect.

The liposomes fuse with the outer surfaces of cells lining the lungs and the DNA passes by natural processes into their nuclei.

Once installed, it will hopefully start making the essential protein that is lacking in CF sufferers.

The method is not as efficient as the more usual gene therapy technique which employs a specially engineered virus to transport the DNA.

However this is unsuitable for the lungs, where there is a high turn over of cells and the possibility of an unwanted immune reaction.

Patients taking part in the trial will undergo the nebuliser treatment once a month for a year.

The liposome technique has been tested successfully in mice, and on human cells in the laboratory.

For safety reasons, the treatment is not being considered for children under 12.

Prof Alton was asked at a briefing for science journalists in London what the chances were of an effective gene therapy being available for Mr Brown's son by the time he reaches that age.

He said: "I think it's very likely we will have some form of gene therapy that will be able to stabilise or prevent some of the symptoms. I would be disappointed if after this effort we don't have something in this time scale."

It was important to be cautious when making predictions and there was still a chance the therapy would not succeed, said Prof Alton. But on the "balance of probability" he thought it was likely to work.

The Cystic Fibrosis Trust has made the gene therapy project a top priority, raising around £18 million of the funding from voluntary donations and by sacrificing research in other areas. The Government, which financed much of the preliminary work, has pledged the remaining £2 million.

Rosie Barnes, the charity's chief executive, said: "Although for new families like the Browns we always want to offer hope and optimism for the future, without this research this remains a very fearsome disease which takes a huge toll on the lives of all those it affects.

"I'm optimistic. We've harnessed the best scientific talent in the UK, and they're very focused. If anybody's able to do it, they are. My view is we've got to keep trying."

Copyright Press Association 2006.