Nuclear Hormones

GSK partnership to show how body clock controls disease

Overview

Inflammatory diseases of the lung are a major cause of mortality world-wide. In the case of Chronic Obstructive Pulmonary Disease (COPD), disease progression is irreversible once it has begun. COPD accounts for approximately 30,000 deaths each year in the UK.

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 6.5% of people in the UK, 7% in the US, and 300 million people worldwide.

Our researchers have teamed up with GlaxoSmithKline to tackle chronic inflammatory disease, and have set up the Manchester Centre for Nuclear Hormone Research in Disease.

Problem

Many inflammatory diseases are highly rhythmic in presentation and are often worse at night. 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.

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.

What we have achieved to date

Working with The University of Manchester and GlaxoSmithKline (GSK), our scientists are investigating how our biological clock controls inflammation in lung diseases such as COPD.

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 team is headed by Professors Andrew Loudon, David Ray and Kath Else, who are working closely with colleagues in the Discovery Biology group at GSK.

In order to develop the drugs, the team are initially studying 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.

We have detailed insight into how the molecular cogs of the clock work, drive cells and physiology. Our researchers have been looking at it organ by organ, cell by cell, unravelling 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.

What we aim to achieve

Our aim is to gain a sufficient understanding of this process so we can target key parts with specific new drugs.

However, 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.

This study is just one at the beginning of an exciting new phase in circadian rhythm research.