THIS WEEK

18 | NewScientist | 5 March 2011

A PIONEERING drug has drastically improved the lung function of people with one type of cystic fibrosis. It is the first to target the cause, not the symptoms, of the world’s most common hereditary lung disease, and combined with a second drug could improve the lives of tens of thousands around the world.

Peter Mueller, chief scientific officer for Vertex Pharmaceuticals in Cambridge, Massachusetts, and colleagues gave the drug, called VX-770, or a placebo to 161 people with cystic fibrosis for a year.

At the outset, most participants

had just 60 per cent of the lung function of a healthy person. At the end of the trial, the lung function of those who had received VX-770 had improved by almost 20 per cent on average; those who received the placebo showed no change. “These data exceeded our expectations,”

said Mueller, announcing the results last week.

No other treatment for cystic fibrosis has led to such dramatic improvements, probably because all have alleviated symptoms rather than attacking the main cause – a defective protein in lung cells called the cystic fibrosis transmembrane regulator, or CFTR. VX-770 is the first drug that fixes the protein itself.

In healthy people, CFTR proteins form channels in the surface membrane of lung and other cells, which shuttle chloride ions in and out of the cell. When they fail, the lungs clog up with mucus, making it difficult for people to breathe and leaving them vulnerable to infections.

VX-770 rectifies a defect in the protein channels in people with a certain form of cystic fibrosis who make a faulty form of the channel that reaches the cell surface but is always closed. By a mechanism that is not yet fully understood, the drug appears to open the channels, says Stuart Elborn at Queen’s University, Belfast, UK, the principal investigator for the European arm of the trial. This allows the amount of liquid on

the surface of the airway to be regulated, so the mucus gets cleared away, he says.

Other benefits included a 55 per cent reduction in the onset of symptoms that require antibiotic treatment, compared with participants receiving the placebo. On average, people receiving the drug also gained around 3 kilograms, suggesting that the disease’s usual effects on digestion had eased.

“It’s pretty exciting,” said a spokeswoman for the UK’s Cystic Fibrosis Trust. “It’s very big news.”

Vertex says it hopes to apply within two or three months to get the drug approved for use in the US and Europe.

One limitation is that only 5 per

cent of people with cystic fibrosis have the mutation that the drug corrects – around 5000 patients worldwide. But Elborn says there is hope for the rest in the shape of a second drug in development, which could correct a mutation affecting 75 per cent of people with cystic fibrosis.

Those with this mutation make the CFTR protein but fail to deliver it to the cell surface. Vertex says that in tests on lung cells in culture, the new drug brings the protein to the surface.

The key could be to combine the two drugs. The company said that a small trial of this combination therapy is already under way, and results are expected within months. n

Andy Coghlan

–Channels need unclogging–

New drug hits root of cystic fibrosis

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“The drug allows liquid on the surface of the airway to be regulated, so the mucus gets cleared away”