Newly Discovered Treatment Using Molecule Inhibitors May Help Rare Kidney Disease

The precise region of PLA2R where antibodies attack has been found, and also the molecules that block antibodies from binding to PLA2R protein.

Scientists at The University of Manchester and Central Manchester University Hospitals NHS Foundation Trust have discovered the cause for a rare kidney disease, Membranous Nephropathy (MN).

Membranous Nephropathy occurs when the immune //system causes antibodies to attack a protein PLA2R that then results in the thickening of the capillary walls in the kidney filters leading to kidney failure.

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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. The team built a three-dimensional model and made 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."

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“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 said “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”.

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Elaine Davies, Kidney Research UK, said that an additional funding has been awarded to further investigate how to stop autoantibody binding using small molecule inhibitors.

Davies added, “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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Source-Medindia