Scientists announce major breakthrough against rare kidney disease
Scientists at the University of Manchester and Central Manchester University Hospitals NHS Foundation Trust have made a significant breakthrough in the fight against Membranous Nephropathy (MN) – a rare kidney disease which can lead to kidney failure. Their research was funded by Kidney Research UK – the UK’s largest funder dedicated to kidney research and kidney problems in the UK.
PLA2R is a protein found in cells in the kidney, and is involved in the development of MN. This disease occurs when the immune system causes antibodies to attack the PLA2R protein which then results in the thickening of the capillary walls in the kidney filters leading to kidney failure.
The team in Manchester have found the precise region of PLA2R where antibodies attack, and have discovered molecules which can block antibodies from binding to the PLA2R protein and causing damage.
Now the team know where the antibody attacks they can design treatments to remove it, or to block it from attacking the kidney with small molecules known as peptides.
80% of adults with MN will produce antibodies against PLA2R, so it was vital for the team to find out how the antibodies bind to the protein and cause damage. To do this, the team needed to know the exact structure of the protein so they built a three dimensional model.
They then discovered that they could stop the antibodies from binding to the PLA2R protein by making a small replica of the binding site so that the antibodies attacked the decoy and not the real protein.
Dr Rachel Lennon commented: “This opens up possibilities for two new treatments for MN patients. We may be able to use a decoy as a drug to block the anti-PLA2R antibodies from attacking the kidney, or we could use small molecules called peptides to remove the anti-PLA2R antibodies from the body.
“Our research should eventually lead to the development of a specific treatment for patients with MN that will reduce the severity of the condition, prevent progression to kidney failure, and reduce the risk to patients from existing immunosuppressive treatment.”
Professor Paul Brenchley says “This research project shows the benefit of University and NHS researchers working closely together to improve treatments for patients. We now know how to remove these damaging antibodies and our research group will develop a specific and safer therapy over the next three years if we can attract the next round of funding”.
Elaine Davies of Kidney Research UK said: “This is a significant breakthrough in the fight against kidney disease and we have awarded additional funding through a PhD studentship announced in April 2015, to Dr Lennon’s team to further investigate how to stop autoantibody binding using small molecule inhibitors. These experiments and the team’s work in general will be vital when developing future treatments for patients with Membranous Nephropathy. However, more funding for research into kidney disease is desperately needed, so we can continue to make important breakthroughs like this which give hope to patients.”
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Notes to Editors:
Membranous Nephropathy (MN) damages the filtering units of the kidney, causing large amounts of protein to leak from the blood into the urine. An estimated 8,400 people have the condition in the UK with 700 new cases a year. 25% of patients will lose their kidney function and need dialysis or a transplant, but the disease can come back in the transplant in a third of patients.
Dr Rachel Lennon is Wellcome Trust Intermediate Clinical Fellow &, Honorary Consultant Paediatric Nephrologist, University of Manchester, and Royal Manchester Children’s Hospital,
Professor Paul Brenchley is Honorary Professor of Renal Immunology, Manchester Royal Infirmary.
Kidney Research UK was founded in 1961 and is the largest funder dedicated to life-saving research into kidney disease in the UK.
Kidney disease is a silent killer and every year more than 55,000 people are treated for end stage kidney failure, 3,000 people die on dialysis, while 350 die waiting for a kidney transplant. Kidney Research UK is dedicated to substantially reducing these numbers through funding life-saving research into kidney disease and by generating public awareness of kidney health.
90 per cent of people on the transplant list are waiting for a kidney, which is more than 6,000 patients. Even though cases of kidney failure are increasing by four per cent every year, Kidney Research UK must turn down four out of every five research proposals it receives due to a lack of funding – proposals which are aimed at enhancing treatments and ultimately finding a cure for kidney disease.
Central Manchester University Hospitals NHS Foundation Trust is a leading provider of specialist healthcare services in Manchester, treating more than a million patients every year. Its eight specialist hospitals (Manchester Royal Infirmary, Saint Mary’s Hospital, Royal Manchester Children’s Hospital, Manchester Royal Eye Hospital, University Dental Hospital of Manchester, Trafford General, Altrincham and Stretford Memorial) and community services are home to hundreds of world class clinicians and academic staff committed to finding patients the best care and treatments. www.cmft.nhs.uk @CMFTNHS
The University of Manchester, a member of the prestigious Russell Group of British universities, is the largest and most popular university in the UK. It has 20 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance. The University is also one of the country’s major research institutions, rated fifth in the UK in terms of ‘research power’ (REF 2014), and has had no fewer than 25 Nobel laureates either work or study there. The University had an annual income of £886 million in 2013/14. www.manchester.ac.uk