Scientists have made a breakthrough in their research for a membranous nephropathy treatment. A team of researchers from the University of Manchester and Central Manchester University Hospitals NHS Foundation Trust has found the precise region of the phospholipase A2 receptor protein (PLA2R) where antibodies attack, and discovered molecules which can block antibodies from binding to the PLA2R protein and causing damage. The research is described in a recent paper, "Identification of a Major Epitope Recognized by PLA2R Autoantibodies in Primary Membranous Nephropathy," published in the Journal of the American Society of Nephrology.

Membranous nephropathy occurs when the immune system causes antibodies to attack the PLA2R protein found in kidney cells, which results in thickening of the capillary walls.  A team of researchers from the University of Manchester and Central Manchester University Hospitals NHS Foundation Trust 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 that researchers know where the antibody attacks, they can design treatments to remove it, or to block it from attacking the kidney with peptides, the researchers said.

About the study
Eighty percent 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, the researchers said. 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.

“This opens up possibilities for two new treatments for MN patients," said Dr.  Rachel Lennon commented. "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."

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