Advantages
- Reproduction of human-like disease mechanisms: The model reproduces the pathogenic mechanism involving anti-nephrin autoantibodies, which are believed to be a major cause of nephrotic syndrome. Because rat glomeruli share many morphological and functional similarities with those of humans, data obtained from this model are expected to have high translational relevance.
- Proprietary anti-nephrin antibody: This nephrin-specific antibody recognizes the functional domain of nephrin, enabling investigation of the dynamics of critical sites. Commercially available anti-nephrin antibodies have low staining affinity for nephrin, and no animal models using them have been reported.
- This highly reproducible and stable model is useful for discovering new therapies and studying nephrotic syndrome and glomerular diseases, and can be applied to drug discovery and efficacy evaluation
Technology Overview & Background
In Japan, more than 350,000 patients are currently receiving hemodialysis therapy due to chronic renal failure, while the number of patients with chronic kidney disease—considered at risk for progression—is estimated at approximately 15 million. Proteinuria not only exacerbates kidney disease but is also associated with over threefold higher risks of stroke and cardiovascular events. Current treatments rely on steroids and immunosuppressants, however, many cases remain prolonged or become severe, highlighting the need for the development of more effective therapies.
The research group has contributed to elucidating the mechanisms of nephrotic syndrome and proteinuria through over 30 years of renal disease research. They discovered that the slit diaphragm of glomerular podocytes is the critical site responsible for the onset of proteinuria. Through their research, they developed an antibody that induces proteinuria in rats simply by intravenous administration. This antibody serves as a valuable model for studying nephrotic syndrome.
Furthermore, recent reports have shown that trace levels of anti-nephrin autoantibodies are a major cause of nephrotic syndrome in humans. Based on these findings, this rat model is expected to serve as a promising system that accurately reproduces human pathophysiology.
Principal Investigator & Academic Institution
Emeritus Professor Hiroshi KAWACHI (Department of Cell Biology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences
Patents
Applied (unpublished)
Data
- The model is established by a single intravenous administration of anti-nephrin antibody to 6-week-old Wistar rats. Proteinuria is induced within 24 hours after antibody injection and peaks on days 5–8.
- The efficacy has been confirmed by administration of drugs such as topiroxostat in this model.
Expectations
The university has deposited the long-used anti-nephrin antibody–producing hybridoma and is currently proceeding with intellectual property rights procedures. We are seeking corporate partners interested in using this model for drug discovery and pharmacological evaluation studies, in addition to selling the model animals and offering contract testing services.
We are open to discuss about various forms of collaboration, such as model sales, joint research, or contract studies.
For more detailed information or inquiries, please feel free to contact us. We are also happy to arrange an initial web meeting with the principal investigator upon request.