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New drug to limit damage to the heart

Published: 
27 April 2006

Scientists at the University of Southampton are part of a UK-wide team involved in the development of a new drug that can limit damage to the heart following a heart attack, and their research features in this week’s edition of the science journal Nature (Thursday 27 April).

A team of structural biologists at the University’s School of Biological Sciences headed by Professor Steve Wood and including Michelle Jenvey, Dr Darren Thompson and Dr Simon Kolstoe participated in the initial design of the new drug and verified its mode of action.

In the Nature article they describe the rational design of the drug molecule that can specifically target a blood protein thought to be a major contributor to the tissue damage that develops following a heart attack. The work is published in collaboration with the Royal Free hospital in London, the Centre for Cardiovascular Science in Edinburgh and the chemistry department at Cambridge University.

The Southampton group used the technique of X-ray crystallography to look at a key inflammatory response protein called C reactive protein (CRP) that binds to cells damaged following heart attack and stroke. CRP normally acts as a molecular flag that marks damaged cells so they can be removed by the innate immune system. However, in conditions such as heart attack so many cells get damaged that entire regions of the heart are destroyed by the bodies own immune system.

The work detailed in today’s paper in Nature describes the design of a chemical compound that can block CRP’s binding to damaged cells after a heart attack, and thus reduce the amount of tissue injury by allowing cells the chance to recover. This suggests that early therapeutic inhibition of CRP might be beneficial for heart attack patients. It also demonstrates the effectiveness of rational drug design as an alternative to more traditional drug discovery techniques.

As with an increasing number of research projects the successful outcome of this work has depended upon the collaboration of a range of experts in fields as diverse as structural biology, organic chemistry and microsurgery. The project has been coordinated by Professor Mark Pepys FRS at University College London.

Notes for editors

  1. Photo caption: Two CRP pentamers viewed down their common five-fold axis, joined together by the new drug compound (blue). One pentamer is shown as a space-filling image (grey), and the other represented as a structural diagram (coloured).
  2. The University of Southampton is a leading UK teaching and research institution with a global reputation for research and scholarship. One of the UK’s top 10 research-led universities, it offers first-rate opportunities and facilities for study and research across a wide range of subjects in humanities, health, science and engineering, and has a strong enterprise agenda. The University has nearly 20,000 students and 5000 staff based across its campuses in Southampton and Winchester. Its annual turnover is in the region of £274 million.
    The University is one of the country’s top institutions for engineering, computer science and medicine. It is home to a range of world-leading research centres, including the National Oceanography Centre, Southampton, the Institute of Sound and Vibration Research, the Optoelectronics Research Centre, the Centre for the Developmental Origins of Health and Disease, and the Mountbatten Centre for International Studies.

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