Treatment breakthrough for smoker's lung'
By Gaia Vince Researchers are starting clinical trials in humans of what they hope may be the first effective treatment for “smoker’s lung” – the UK’s fourth biggest killer – after the therapy showed success in mice. Chronic obstructive pulmonary disease (COPD) is a condition describing a range of severe inflammatory diseases of the lungs including chronic bronchitis and emphysema. More than 90% of cases are caused by cigarette smoking, and even when a smoker quits the habit, the disease continues, becoming progressively worse – often until the patient dies from respiratory failure. COPD currently kills more than 30,000 people in the UK every year and is predicted to kill over six million worldwide by 2020, becoming the world’s third biggest killer. To date, it has only been possible to ease the symptoms of COPD. Researchers have failed to understand why steroids – an effective treatment for asthma-related lung inflammation – have proved ineffective in treating COPD. Now, scientists at Imperial College London, UK, have taken the first step towards a cure for the fatal disease by discovering why it is resistant to steroid treatment. Peter Barnes, professor of thoracic medicine, and colleagues examined the role of an enzyme in the lung cells called HDAC2, which “switches off” the genes responsible for causing inflammation. Usually, steroidal drugs are able to facilitate this process by providing a molecular pathway between HDAC2 and the appropriate genes. But Barnes discovered that levels of HDAC2 were very low in COPD patients, which was why steroids had little effect. “Smoking causes oxidative stress in the cells, which results in reduced production of HDAC2 and much of the enzyme is in a deactivated form so it doesn’t respond to treatment by steroids,” Barnes explains. He realised that by administering low doses of a cheap and widely available drug – theophylline – he could boost the levels of the enzyme, and therefore enable steroids to treat COPD. “Theophylline is a bronchodilator that has been used for the past 70 years in asthma and COPD patients, but until now it has always been administered in very high doses. We found that in very low doses the drug has a different effect – it appears to activate HDAC2 and increase its production. “We should be able to prevent people with COPD getting worse and hopefully allow them to recover,” Barnes says. Steve Connellan, chair of the British Thoracic Society COPD consortium, calls the research exciting, but cautions: “Time will tell as to whether this research which analyses complex changes down at the cellular level of our bodies will be successfully translated into real benefits for patients with smoking-related lung disease.” The UK team has successfully tested the two-drug treatment in mice and is about to begin clinical trials in 40 patients. And the therapy may have further benefits. “We are collaborating with researchers in other inflammatory diseases such as rheumatoid arthritis and psoriasis, where patients have ceased to respond to steroids, to see whether low doses of theophylline could potentially benefit these patients too,” Barnes says. The research will be presented at the British Endocrine Society meeting in Harrogate, UK,