New drugs being tested in the US may help Irish cystic fibrosis sufferers, writes Claire O'Connell
THEY MAY not sound like much, but the codes PTC124 and VX-770 could be highly important to people with cystic fibrosis (CF). They are the rather unglamorous names of two drugs that have recently delivered encouraging results in trials to address the underlying genetic causes of the condition.
And while these drugs may ultimately benefit only a limited number of the approximately 1,200 CF patients in Ireland, they highlight the potential of emerging therapies, according to the chief executive of the Cystic Fibrosis Association of Ireland, Godfrey Fletcher.
Per head of population, Ireland has the highest number in the world of people with CF, an inherited condition where a problem with salt regulation results in mucus building up in the lung and other organs, he explains.
"Cystic Fibrosis expresses itself firstly in the thick secretion of mucus in the lungs, which will block off the bronchioles and then you get an anaerobic bacteria breeding in these closed cavities within the lungs which causes major damage to the lungs themselves," he says.
"But CF is also active in the liver, the digestive system and the pancreas. A lot of people with CF have diabetes, they have to take digestive enzymes and certain gene mutations are more aggressive towards liver damage."
Currently people with CF undergo a number of treatments to manage the disease, including infection control, physiotherapy and nutritional therapy. Some eventually have a double-lung transplant.
But now new drugs are being trialed to target the underlying causes. People with the disease have one or more mutations in the gene for the chloride-regulating channel CFTR, and some new therapies aim to tackle the problem.
Earlier in the summer PTC124 caused a stir when researchers from Israel announced that in human trials the drug appeared to successfully overcome a "nonsense" genetic variation that prevents the CFTR gene from being properly switched on, and leads to the disease.
However, only around 3 per cent of the Irish CF population carry such nonsense mutations, according to Fletcher.
Meanwhile VX-770, which is being trialed by US company Vertex Pharmaceuticals, appears to successfully target another genetic mutation in the chloride channel gene that crops up in around 11 per cent of Irish people with CF, he adds.
And even more encouragingly another drug, VX-809 (also from Vertex), is in early Phase I trials to correct the damage caused by the most prevalent mutation that appears in Ireland. "If it shows positive results it could have a much greater positive effect for Irish patients, as it addresses the delta 508 mutation which presents itself in approximately 89 per cent of the Irish [CF] population," says Fletcher.
"It's very positive," he adds, noting that commentators believe drugs in the pipeline could eventually push life expectancies of CF patients up from the thirties to the fifties or sixties.
He would like Ireland to play an active role: "We are talking to pharmaceutical companies to try to develop Ireland as a centre for clinical trials.
"This is because, with clinical trials, as well as being on the cutting edge of new breakthroughs, in the hospital environment if clinical trials are taking place it is a known fact that the quality of care goes up, because there has to be increased monitoring of the patients, even if they are taking placebos."
However, any new drugs will be of little use unless CF patients also have the proper care environment, he notes. "It is very encouraging, but even if these therapies are available, we have to have the correct facilities and staff in place in order to implement it.
"There's no point in having these great drugs there if people are being subjected to cross-infection in the wrong type of hospital facilities."
That's why Fletcher welcomes the opening of eight interim beds for CF patients in St Vincent's University Hospital in Dublin last month, and that building will soon start on a dedicated CF unit, which is scheduled to open in 2010.
"It is fantastic news, but this is something which has to be mirrored in different centres around the country, it can't just be St Vincent's," he says. "We are already working with Crumlin Hospital to build four single rooms en suite, planning has already started on that, and we are working in Cork University Hospital and Galway University Hospital to get things to happen as well, because it has to be a national issue."