New use for old drugs in treating hepatitis C?
7 June 2010
BBSRC-funded research shows that common drugs used to treat conditions such as diabetes and obesity could be used to successfully treat hepatitis C virus infection.
Research led by the University of Leeds has found drugs such as anti-diabetic drug Metformin and AICAR, used to combat obesity, can prevent the hepatitis C virus from replicating in the body.
Hepatitis C virus affects an estimated 3% of the world's population and there are 4M carriers of the virus in Europe alone. The virus affects the liver and recovery rates are low: only around 40% of hepatitis C sufferers will fully recover, with others developing cirrhosis and in many cases, liver cancer(1).
"We're very excited about these findings," says Professor Mark Harris from the University's Faculty of Biological Sciences. "These drugs are already on the market, and whilst substantial clinical trials still need to take place before they can be used to treat hepatitis C infection, we think it could be an enormous step forward in the battle against the virus."
The research was supported by the Wellcome Trust, the Medical Research Council and the Biotechnology and Biological Sciences Research Council.
Drugs such as Metformin and AICAR work by stimulating an enzyme called AMP kinase (AMPK) which regulates energy within our cells - the very enzyme that hepatitis C virus represses to enable it to replicate.
AMPK's usual function is to conserve the energy balance in cells, which it does by temporarily shutting down the production of lipids (fats) and membranes when it senses an increase in energy requirements. Professor Harris and his team have now shown that the hepatitis C virus switches off AMPK so that the cell continues production of lipids and membranes, both of which are vital to its survival.
"You'd expect AMPK to be activated when a cell becomes infected by a virus, because it would sense the increase in energy required to enable the virus to replicate. In such cases, AMPK would shut down certain functions of the cell temporarily until the cell's energy is rebalanced," says Professor Harris. "We found that hepatitis C virus, because it needs lipids and membranes, causes the opposite to happen."
Building on this finding, the research team were able to examine how cells would react when treated with common drugs that stimulate AMPK. They found that in infected cells, the drugs were able to halt virus replication, enabling cells to clear the infection.
A patent has been filed on the discovery and the team will shortly embark on a small-scale clinical trial with the University of Nottingham. This will provide a greater evidence base upon which future clinical trials can be based.
Mair Hughes, a PhD student working on the project, is funded by a Biotechnology and Biological Sciences Research Council (BBSRC) CASE studentship, which is funded jointly by BBSRC and pharmaceutical company Arrow Therapeutics. These Collaborative Awards in Science and Engineering (CASE) allow students to receive high quality research training in collaboration with an industrial partner.
Notes to editors
This research is published in a paper entitled Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase in the latest edition of Proceedings of the National Academy of Science (PNAS). A copy of the paper is available on request.
The research contained within this paper was supported by the Wellcome Trust, the Medical Research Council and the Biotechnology and Biological Sciences Research Council.
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About the Faculty of Biological Sciences
The Faculty of Biological Sciences at the University of Leeds is one of the largest in the UK, with over 150 academic staff and over 400 postdoctoral fellows and postgraduate students. The Faculty is ranked 4th in the UK (Nature Journal, 457 (2009) doi :10.1038/457013a) based on results of the 2008 Research Assessment Exercise (RAE). The RAE feedback noted that "virtually all outputs were assessed as being recognized internationally, with many (60%) being internationally excellent or world-leading" in quality. The Faculty's research grant portfolio totals some £60M and funders include charities, research councils, the European Union and industry. http://www.fbs.leeds.ac.uk.
About the University of Leeds
The 2008 Research Assessment Exercise showed the University of Leeds to be the UK's eighth biggest research powerhouse. The University is one of the largest higher education institutions in the UK and a member of the Russell Group of research-intensive universities. The University's vision is to secure a place among the world's top 50 by 2015. http://www.leeds.ac.uk.
About the Wellcome Trust
The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk.
About the Medical Research Council
For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk.
About the University of Nottingham
The University of Nottingham is ranked in the UK's top 10 and the world's top 100 universities by the Shanghai Jiao Tong (SJTU) and the Times Higher Education-QS world university rankings.
Research Fortnight analysis of Research Assessment Exercise (RAE) 2008 ranks Nottingham 7th in the UK by research power.
More than 90% of research at The University of Nottingham is of international quality, according to RAE 2008, with almost 60% of all research defined as 'world-leading' or 'internationally excellent'.
Twice since 2003 its research and teaching academics have won Nobel Prizes.
The University provides innovative and top quality teaching, undertakes world-changing research, and attracts talented staff and students from 150 nations. Described by The Times as Britain's "only truly global university", it has invested continuously in award-winning campuses in the United Kingdom, China and Malaysia.
The University won the Queen's Award for Enterprise in both 2006 (International Trade) and 2007 (Innovation - School of Pharmacy), and was named the first 'Entrepreneurial University of the Year' at the Times Higher Education Awards 2008-2009.
BBSRC is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £470M in a wide range of research that makes a significant contribution to the quality of life in the UK and beyond and supports a number of important industrial stakeholders, including the agriculture, food, chemical, healthcare and pharmaceutical sectors.
BBSRC provides institute strategic research grants to the following:
- The Babraham Institute
- Institute for Animal Health
- Institute for Biological, Environmental and Rural Studies (Aberystwyth University)
- Institute of Food Research
- John Innes Centre
- The Genome Analysis Centre
- The Roslin Institute (University of Edinburgh)
- Rothamsted Research
The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.
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