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Extending the life of the transplant

A picture of the kidneys

Experts from the Medical Research Council (MRC) Centre for Transplantation at King’s have revealed exciting new scientific developments for people with an organ transplant, intended to help prevent rejection of the new organ and extend its life. Watch a video of the research.

They discussed two pioneering areas of research, at an event at the British Science Festival in Birmingham, that they hope will have a significant impact on transplant medicine and patients in future - techniques known as protein therapeutics and cell therapy.

Although organ transplantation has been taking place for over 50 years, there are a number of significant challenges, such as a shortage of donor organs, maintaining the quality of an organ in transit, and the risk of organ rejection both immediately after transplant and in the following years.

The event entitled ‘Extending the life of the transplant’ was facilitated by broadcaster and writer Vivienne Parry. Sue Townsend, author of the Adrian Mole books, spoke about her experience as a recipient of a donor kidney and gave away copies of a new Adrian Mole short story, which she had written especially for the debate.

Protein therapeutics

The work using protein therapeutics aims to reduce the risk of an organ being damaged in the hours and days following a transplant, by maintaining the quality of the donor organ prior to transplantation.

Currently, organs cannot survive outside the body for more than around 24 hours. In daily life when an infection or virus meets cells or fluids in the body, it activates a part of the immune system, known as the ‘complement’ system, which attacks and attempts to destroy the cells of the intruder organism.

The complement system is usually kept in check by ‘regulators’ which are found on the surface of the cells. Their presence prevents it from attacking the body’s own cells. However, when an organ is removed for transplantation, complement regulators are lost from the surface of cells due to the lack of blood flow and consequent lack of oxygen. Unregulated, the complement system begins to attack the organ’s own cells, severely damaging it. Once the transplant is complete, the effect can be amplified as the complement system supports the recipient’s own blood cells in its attack on the organ – resulting in organ rejection.

Working with the biotechnology industry, scientists at the MRC Centre for Transplantation have evolved a method for ‘painting’ the inner surface of donor kidneys with a protective layer made from a substance which is a natural regulator of these proteins in humans.

Dr Richard Smith, Director of the Protein Therapeutics Laboratory, said: ‘We have engineered a protein Mirococept to combat organ damage during transit outside the human body and immediately after transplantation.  It is an artificial replacement for complement regulators. If enough Mirococept proteins reach the organ’s cell membranes, it can prevent the complement cascade from starting and increases the number of donor organs suitable for transplantation.’
 
Cell therapy

The other exciting area of research is a type of potential treatment scientists hope will improve the longevity of a transplant.

Currently, transplant recipients have to stick to a strict regimen of potent drugs that pacify the immune system in an attempt to prevent rejection of the donated organ. However, because these drugs suppress the immune system, they sometimes bring serious health complications, such as infections and some types of cancer.

The scientists are looking at other ways of prolonging the life of a transplant, which involve using a type of white blood cell – regulatory T cells found in healthy individuals – as a treatment to prevent an individual’s immune system from becoming over active and rejecting the organ.

Professor Giovanna Lombardi, Professor of Human Transplant Immunology, said: ‘Animal studies have already shown that these cells can effectively prevent a transplant being rejected. We are currently identifying ways to ‘grow’ these cells from the blood of healthy individuals in the laboratory without them losing their ability to suppress other immune cells and are carrying out a study of the number and quality of regulatory T cells from patients on the waiting list for a kidney transplant. We are optimistic that we will be able to carry out the first clinical trials in transplant patients in the next few years.’

These two areas of research at the MRC Centre for Transplantation form part of a exciting and wide ranging programme of liver, kidney, pancreas and bone marrow transplantation research taking place across King’s Health Partners Academic Health Sciences Centre.

Professor Steve Sacks, Director of the MRC Centre for Transplantation said: ‘King’s Health Partners is at the leading-edge of transplant research internationally, with a strong focus on translational research. We are studying a number of areas, ranging from ways to improve the matching of patients to donor organs to improve the lifespan of donated organs, ways to better predict transplant outcomes, and to personalise the amount of immunosuppression individual transplant patients need to take. This translational research will bring real benefits to our patients and others further afield.’

Notes to editors

The MRC Centre for Transplantation at King’s hopes to launch clinical trials for both of these potential treatments in 2011. Further information will be available on the BRC website once these studies receive positive ethical approval to take place.

For further information about the MRC Centre for Transplantation visit http://transplantation.kcl.ac.uk/

British Science Festival
The British Science Festival is one of Europe's largest celebrations of science, engineering and technology, with over 250 events, activities, exhibitions and trips taking place over a week in September. The programme of events offers something for everyone with activity for families and schools groups, adults looking for entertainment and stimulating debate or professionals interested in the latest research. http://www.britishscienceassociation.org/web/BritishScienceFestival/

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

King's College London
King's College London is one of the top 25 universities in the world (Times Higher Education 2009) and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,000 students (of whom more than 8,600 are graduate students) from nearly 140 countries, and some 5,500 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.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: www.kingshealthpartners.org.

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