Scientists at The University of Manchester and Central Manchester University Hospitals NHS Foundation Trust have made a tremendous breakthrough in combatting Membranous Nephropathy (MN), which is a highly rare kidney disease that often leads to kidney failure. The scientist’s research was largely funded by the Kidney Research UK, which is the United Kingdom’s biggest funder in matters relating to kidney research and kidney disorders/diseases in the UK.
Throughout the course of their research, the scientists discovered a protein known as PLA2R. This protein, which is found in the kidney, has been discovered to have a direct hand in developing the rare MN disease. Essentially the disease occurs just as the immune system discharges antibodies to attack the PLA2R protein which then leads to the thickening of the capillary walls in the kidney filters, which in most cases eventually results in kidney failure.
The major breakthrough is due to the fact that this team of Manchester scientists have determined the exact location of where this PLA2R protein stems from and have found the molecules which can obstruct antibodies from effectively neutralizing the PLA2R protein resulting in damage to the kidney(s). Therefore, since the team knows precisely where the protein comes from and where the antibodies attack they can then implement treatment courses that can remove it, or prevent it from assaulting the kidney with smaller molecular agents known as peptides.
“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,” stated lead author Dr. Rachel Lennon.
Approximately 80 percent of adult patients diagnosed with MN naturally produce antibodies that combat PLA2R. Therefore, it was paramount that the team discover how these antibodies latched onto the protein and did more harm than good. In order to complete such a task the team constructed a three dimensional model of the protein. By using their three dimensional model, the team was able to devise a method that could stop antibodies from attaching itself to the protein by building a smaller replica of the binding site so that the antibodies would attack the decoy instead of the actual protein.
“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,” noted Lennon.
Furthermore, Head of Kidney Research UK, Elaine Davies applauds the new discovery; as it has all the necessary groundwork that can be used to eradicate an otherwise incumbent disease.
“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.”
