As a recipient, Dr. Borza will receive $250,000 over two years towards his research project, which looks to develop new blood tests that can identify specific antibodies involved in this kidney disease.
“I am both happy and proud that my NephCure Grant application has been selected for funding this year. Previous awardees have made seminal contributions to understanding the pathobiology of nephrotic syndrome and paving the way for innovative treatment options. I feel humbled to join their ranks,” said Dr. Borza.
Membranous nephropathy (MN) is a kidney disease where the body’s immune system mistakenly attacks the kidneys, causing a major loss of protein in the urine. This happens because the immune system creates harmful antibodies that latch onto certain proteins in the kidney and damage the filter that cleans the blood.
For many years, doctors only knew about one main protein (PLA2R) that these antibodies target in most patients. But new scientific tools have helped researchers discover many more target proteins. Each of these proteins is linked to different forms of the disease, which means doctors can better understand what’s causing it and choose treatments that are more personalized and effective.
Right now, identifying which protein is being attacked usually requires a kidney biopsy, an invasive procedure. Blood tests are available for only two of the known proteins.
This project aims to change that. Using large national collections of patient samples, researchers will create and test new blood tests that can detect antibodies for the newly discovered proteins.
If successful, doctors will be able to diagnose and monitor the disease with a simple blood test instead of a biopsy. Tracking these antibodies over time may also help doctors see whether treatments are working or if the disease might return.
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NephCure’s mission is to ensure that all individuals with rare, protein-spilling kidney disease have equitable access to the care and treatments that offer them the best kidney health outcome possible. Founded in 2000 by a group of committed patient parents, NephCure has invested more than $40 million in kidney disease research and helped create a landscape where there are now new treatments and more than 60 interventional drug trials for rare kidney diseases. NephCure is a U.S. tax exempt 501(c)(3) public charity.
Project Summary
Membranous nephropathy (MN) is an immune-mediated kidney disease in which patients develop an abnormal, massive loss of blood proteins in urine (proteinuria). The disease occurs when the immune system abnormally produces autoantibodies that mistakenly attack body’s own proteins (antigens) in the kidneys. Upon binding to target antigen, the autoantibodies form immune complexes that lodge within the kidney sieve that filters blood to produce urine, causing damage. After the initial identification of PLA2R as the most common antigen targeted in two-thirds of patients with MN, recent technical advances resulted in the discovery of about a dozen additional new antigens. Because different kinds of MN associated with different antigens have distinctive clinical associations, a newly introduced antigen-based classification of MN allows for a “precision medicine” approach, which helps to identify the specific underlying cause, enabling tailored and more effective treatment strategies.
However, the antigen-based classification of MN currently requires an invasive kidney biopsy, because clinical tests for detecting autoantibodies in patients’ sera are only available for PLA2R (as well as THSD7A, the second antigen identified). This project will leverage the unique resources provided by the NEPTUNE and CureGN biorepositories to develop and validate novel serologic tests for autoantibodies targeting other recently discovered MN antigens. We expect that serology-based antigen classification of MN will reduce the need for an invasive kidney biopsy. In addition, monitoring the serum levels of autoantibodies and how they change over the course of disease can be used to monitor disease activity, response to treatment, and provide advanced warning of disease recurrence.
