Induction of neutrophil apoptosis and treatment of severe lung inflammation

Inflammatory lung diseases like chronic bronchitis and emphysema (COPD) and scarring conditions are responsible for a huge burden of illness and untimely deaths in the UK, but current treatments are at best poorly-effective. Over the past twenty years we have been taking an alternative approach to harness the mechanisms by which some inflammatory responses are known to get better spontaneously. Specifically we have identified a mechanism by which key inflammatory cells called neutrophils can be made to commit suicide and be removed silently by local scavenger cells called macrophages. Unfortunately this suicide process is usually overcome by powerful survival factors present in the inflamed lung. In work newly-published in the leading international medical science journal Nature Medicine we have shown that a CDK inhibitor called R-roscovitine, currently under clinical trial in cancer patients, causes a hitherto unexpected induction of neutrophil suicide, even in the presence of survival factors, and makes relevant models of human inflammatory lung disease resolve. This work has recently been publicised in the lay press. In our proposed programme of research we will define exactly how this works, an approach which may lead to the discovery of other useful anti-inflammatory drugs. We will also carry out a clinical study of the drug s effectiveness using cutting-edge imaging technology to monitor the progress of the disease non-invasively and demonstrate its response to treatment.