Breathing new life into the treatment of cystic fibrosis

Anders Gibson is excited about the gene therapy research
Anders Gibson is excited about the gene therapy research
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THE sun streams through the windows, lighting up the laboratory and giving rather ordinary-looking beakers, petri dishes and test tubes a touch of sparkle.

Despite the momentary glow, the atmosphere continues to be one of quiet concentration. There’s no hint here of any rush, of working against the clock, of a deadline looming, even if that’s exactly what the white-coated scientists are facing: a cruel clock which speeds up the closer those who suffer from cystic fibrosis (CF) get to their 40th birthdays.

They may seem relaxed, but Dr Chris Boyd and his team, based in a nondescript building at the Western General’s Molecular Medicine Centre, are all too aware of the pressure they are under. Their pioneering research into gene therapy could ultimately make the fatal lung disease as controllable as asthma, with just a daily puff from an inhaler – replacing faulty genes with normal ones and treating the condition rather than the symptoms.

“In fact, if it works the way we hope it will, then it could mean that in future CF patients will not have to take all the medication they currently do, or need the physiotherapy they have to undergo,” says Dr Boyd.

“Ultimately, we hope gene therapy will push CF patients towards normal life expectancy and improve their quality of life significantly. To reduce it to something like asthma, to be able to treat it in that way, would be a magnificent outcome.”

That concept is the Holy Grail and Dr Boyd talks of caution in their approach, but it’s no longer a far-fetched idea. After all, years of work into new antibiotics and drug treatments has seen the average life span of a CF sufferer increase from the teens to the late 30s.

It’s an age most with the condition still never dare to hope to reach.

Cystic fibrosis is the most common lethal inherited disease in the UK, caused by a mutant gene which prevents cells from producing healthy digestive juices, sweat and mucus. These fluids become thick and sticky and clog up lungs and digestive tracts, which then become infected and damaged.

Around 150 children a year are born with the disease – including James Fraser Brown, the now four-year-old son of Gordon Brown.

Now Dr Boyd and his team – the Edinburgh University third of the UK Cystic Fibrosis Gene Therapy Consortium, the other two thirds being in Oxford and London – are about to launch the largest trial of its type in Britain, involving 130 patients, half of whom will be from Scotland.

Patients, aged 12 and over, will receive one dose of the treatment every month for a year, inhaling molecules of DNA wrapped in fat globules.

“This will deliver the normal gene into the cells in the lung lining,” says 55-year-old Dr Boyd. “And because it’s a working copy of the gene it will replace the function of the defective gene which has caused the CF.

“Gene therapy works by replacing faulty genes with normal ones. It’s not a new concept and we’ve been working on refining it for ten years, but this is the first clinical trial where we will be giving this treatment through a nebuliser and patients will have 12 doses in a year, so we hope to see a real difference at the end. And given the age of the patients involved, the Sick Kids hospital is also on board.”

He adds: “We’ve been through phase one of the trial, giving patients one dose of the DNA therapy to test for safety and it’s proved safe. This, the largest trial of its type, is phase two.”

However, the trials nearly never happened. Last year, just for phase one, the Cystic Fibrosis Trust, which funds the consortium, launched a Six Million in Six Weeks appeal to raise the money to get things started.

While that was a huge success and raised enough to get phase one completed, shortly afterwards the recession began to bite and it looked as though phase two would never happen. Two weeks ago, however, the Medical Research Council (MRC) and National Institute for Health Research stepped in with a £3.1 million grant.

“Even more importantly the MRC gave us a further £1.2m to fund the next step,” says Dr Boyd. “We are already working on a better delivery system to get the normal gene into the lung lining rather than using a fat globule and that will be many more years in research.

“What we’re doing is looking at introducing the genes to the lungs through a modified virus. We would remove all the genes which make a virus dangerous and replace them with a working copy of the CF gene, and we know from studies we’ve done already that it’s better at getting into the lung cells than the fat. After all, viruses have evolved to get into cells quickly.”

The problem his team faces is making enough of the virus as growing one is an incredibly sophisticated process. Using small petri dishes in the lab is one thing, but one patient alone might need 1000 petri dishes’ worth of the virus for the treatment to be effective. “We’re going to need a bigger tank,” he smiles. “That’s the next step.”

Dr Boyd has been working in the field for 15 years, while others in the consortium have been focused on CF for even longer.

“Medical research always takes longer than you want because it is difficult, especially with complex diseases like CF,” he admits. “A lot of other conditions already have treatments because it was easy to find a drug – that’s not been the case with CF.

“But there is a lot of hard work going on, and we’re very grateful for the funding we receive.”

He adds: “This trial is a coup for Scotland. There are only two places where the therapy will be available, and Edinburgh is one. That’s a big deal.”

n Cystic Fibrosis Week this year runs from April 29 to May 5. On May 2, the CF Trust will be inviting MSPs to test their lung function, to raise awareness of the charity.