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New study to show how our body clock controls disease

New treatments for inflammatory lung diseases and a host of other conditions could be developed following a study into the impact of circadian rhythms - or body clock.

In a partnership between The University of Manchester, the NIHR Manchester Biomedical Research Centre and GlaxoSmithKline (GSK), a team of scientists will investigate how our biological clock controls inflammation in lung diseases such as Chronic Obstructive Pulmonary Disease (COPD). It is hoped that this project, worth more than £500,000, will lead to the development of new drugs which will target how the internal body clock regulates the severity of inflammation.

The Manchester team is headed by Professors Andrew Loudon, David Ray and Kath Else, and they will work closely with colleagues in the Discovery Biology group at GSK. Inflammatory diseases of the lung are a major cause of mortality world-wide. In the case of COPD, the progression of this inflammatory disease is irreversible once commenced. In the UK 27,478 people died as a result of COPD in 2004. Other diseases with an inflammatory aspect include asthma, which is a predisposition to chronic inflammation of the lungs in which the airways are reversibly narrowed. This disease affects 7% of people in the US, 6.5% in the UK and 300 million people worldwide, and causes 4,000 deaths a year in the US.

In order to develop the drugs, the team will first study the mechanisms whereby the circadian clock controls the magnitude of the local inflammatory response; that is, the genes and pathways that connect the clock to the cells responsible for the immune response in the lungs. Professor Loudon, of the Faculty of Life Sciences, explains: "Many inflammatory diseases are highly rhythmic in presentation and often worse at night."

"We believe there is also a strong rhythmic control. It has long been speculated that asthma and other inflammatory conditions have an underlying clock mechanism controlling the severity of the disease. These clocks are all over the body, including in cells responsible for the immune response in the lung. In addition the way we metabolise drugs is highly rhythmic.

"Our aim is to gain a sufficient understanding of this process so we can target key parts with specific new drugs. "We are working with GSK not only to develop new drugs to alleviate symptoms but also reveal optimal timing of therapy, known as chronotherapy. This is a new and exciting area of research. It is being taken very seriously in France, for example, where researchers have for some time been studying the importance of timing of chemotherapy in cancer."

He adds: "After a decade of research into the area you don't have to explain to anyone what the circadian clock is these days, which is a very good thing. But in the last three years we have gone further, developing very strong links between the basic science and its clinical application. "We have detailed insight into how the molecular cogs of the clock work, drive cells and physiology. We have been looking at it organ by organ, cell by cell, unraveling how the clock drives the biology of the organism. Many diseases are rhythmic, so it's no surprise that when the circadian rhythm is disrupted it is associated with altered physiology. "This study is just one at the beginning of an exciting new phase in circadian rhythm research."