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Scientists target enzyme in bis to takle chronic kidney disease

Nottingham Trent UniversityNew research which aims to tackle chronic kidney disease is underway at Nottingham Trent University. Scientists are investigating the enzyme Transglutaminase-2 (TG2) – known to be responsible for kidney scarring and failure – to see how it can be targeted and blocked before serious problems occur.

It is hoped that, for the first time, the project could lead to the development of new drugs capable of halting the progression of kidney disease – a gradual irreversible damage to kidney function, for which there is no cure. The work is being funded by national charity Kidney Research UK.

The disease, which costs the NHS £3.66bn a year, is thought to be getting more common because of its links with Type 2 diabetes, the result of increasing problems of obesity and ageing societies.

The research team, based in the university’s School of Science and Technology, is working in close partnership with the University of Sheffield’s Kidney Institute to identify factors responsible for the unique mechanism by which TG2 is exported from cells in kidney disease.

Using an approach developed in-house, they are investigating the various proteins associated with the enzyme so they can assess the best ways of interfering with its export from the cell in kidney disease – an event that causes a progressive scarring of the kidney and ultimately its failure.

The results of the 18 month study could lead to major advances in the development of other anti-scarring drugs, capable of treating a range of other conditions.

This latest study is the continuation of more than 15 years’ work examining the role and behaviour of TG2 at Nottingham Trent University.

Causes of kidney injury include diabetes, autoimmune disease and high blood pressure, regular use of certain medications and prolonged infections or primary kidney diseases.

Scarring occurs when the body’s wound-healing fails after sustained or ‘chronic’ injury. After a first injury the kidney undergoes a physiological repair process to recover, however sustained injury results in excessive wound repair and scar formation, similar to that seen in the skin. If the repair process is sustained, it leads to scarring and loss of kidney function.

Lead scientist, Dr Elisabetta Verderio Edwards, who runs the Transglutaminase Research Team at Nottingham Trent University, said: “The long term goal of our research work with the Sheffield Kidney Institute is to be able to block TG2 and to prevent the detrimental consequences of its activity during chronic kidney damage. This will ultimately allow for the development of new therapies for kidney disease.”

Lead nephrologist, Dr Tim Johnson, an international expert in TG2 and kidney disease, based at the University of Sheffield, said: “It’s fantastic that we have obtained this funding. It allows us to continue our long collaboration with Nottingham Trent University on this work.

“TG2 has proved to be a very difficult enzyme to target specifically. This approach to identify binding partners for TG2 in its cell export may allow us to develop therapeutics that could lock TG2 in the cell and thus prevent its harmful effects once released.

“This would have a dramatic effect on the long term prognosis of our patients.”

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