Researchers at King's College London have identified a new gene (PIM1), which could be an effective target for innovative treatments and therapies for the human autoimmune disease, psoriasis.
Psoriasis affects around 2 per cent of people in the UK and causes dry, red lesions on the skin which can become sore or itchy and can have significant impact on the sufferer's quality of life.
It is thought that psoriasis is caused by a problem with the body's immune system in which new skin cells are created too rapidly, causing a build up of flaky patches on the skin's surface. It is not known exactly why this problem occurs but it is thought that certain genes may play a role.
The study, published today in Science Translational Medicine highlights for the first time the role of PIM1 and the IL-22 cytokine - a protein that sends messages between cells - in skin inflammation such as that seen in psoriasis patients.
Scientists, led by Professor Frank Nestle from the St John's Institute of Dermatology at Guy's and St Thomas' NHS Foundation Trust and King's College London, injected IL-22 into models of normal human skin in mice.
The changes that subsequently occurred in the skin were reminiscent of psoriasis. Injecting an antibody to block the IL-22 cytokine caused these changes to reverse.
They were then able to perform computer analysis, comparing the data from these human skin models with existing gene datasets, in order to identify the gene PIM1 as one of the genes 'switched on' by the presence of IL-22. They further showed that a small molecule drug blocking PIM1 was effective in models of psoriasis. The link between the IL-22 cytokine, which causes inflammation, and subsequent changes in the PIM1 gene suggests a direct link between PIM1 and psoriasis.
It is the first time that this gene has been identified as having a specific link to the condition. The combined use of computer analysis of complex gene data sets and disease relevant human skin models, also called integrative biology, is innovative and means that research can be more easily translated to further clinical studies for patient benefit. This new type of approach will likely generate more insights into disease mechanisms but also new drugs for the treatment of psoriasis, thereby reducing the gap between discovery and the clinic
Professor Nestle said: 'We have been able to confirm that the protein IL-22 causes inflammatory changes in human skin contributing to psoriasis.
The most exciting part of the study was that detailed analysis of genes induced by IL-22 in skin allowed us to uncover a novel treatment target for this disease. We are hopeful that our research will lead to the development of new approaches for the treatment for this common and irritating skin condition.'
The authors say that whilst this is a significant development providing proof of principle in pre-clinical models of disease, further research, in the form of clinical trials, is necessary in order to test potential new treatments for effectiveness in humans. However, as the findings are easily transferable to clinical studies, the discovery of this new gene target has promise for the development of new drug therapies.
The study was supported by the Medical Research Council, Wellcome Trust and the National Institute for Health Research Biomedical Research Centre (NIHR BRC) at Guy's and St Thomas' NHS Foundation Trust and King's College London.
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Notes to editors:
King's College London
King's College London is one of the top 20 universities in the world (2013/14 QS World University Rankings), and the fourth oldest in England. It is The Sunday Times 'Best University for Graduate Employment 2012/13'. A research-led university based in the heart of London, King's has more than 25,000 students (of whom more than 10,000 are graduate students) from nearly 140 countries, and some 6,500 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.
King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.
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About the National Institute for Health Research
The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website.