Kidney Disease


Nephrin

Nephrin is a newly discovered protein, which is a key component of the kidney's ultrafiltration barrier, and a promising new molecular target for the treatment of proteinuria, a common symptom of most kidney diseases.

The laboratory of Dr. Karl Tryggvason, a cofounder of BioStratum, discovered the genetic defect that causes the disease congential nephrotic syndrome. The identified gene encodes for a protein named nephrin that has subsequently been determined to be the structural component of the slit diaphragm, the structure that links the podocyte pedicels (glomerular epithelial foot processes) at the interface with the glomerular basement membrane. The slit diaphragm, along with the fenestrated vascular endothelial cells and glomerular basement membrane, constitute the kidney's ultrafiltration barrier.

The massive proteinuria that develops in the absence of a functioning nephrin molecule indicates the critical role that this protein plays in the ultrafiltration barrier. Mutations in other proteins that comprise the kidney's ultrafiltration barrier do not lead to such massive proteinuria. While congenital nephrotic syndrome is a relatively rare disease, proteinuria is a common consequence of most glomerular diseases. Thus we believe therapeutics that increase the expression of nephrin may lead to an effective treatment
for proteinuria. We are continuing our research on this promising therapeutic target, studying the genetic determinants that control its expression, and examining
its potential role in mediating other kidney diseases.

Diabetic Nephropathy Susceptibility Gene

BioStratum scientists are searching for the gene that makes a diabetic patient susceptible to developing kidney disease (nephropathy). The identification of the diabetic nephropathy susceptibility gene(s) and the protein(s) they encode could provide researchers with the identity of biochemical pathways and targets that play a significant role in the disease process, pointing the way for potential new and improved therapeutic approaches. In addition, the determined genetic susceptibility factors could provide for
a DNA-based test to evaluate the propensity of diabetic patients to develop kidney disease. Diabetic patients
who screen positive for this gene(s) are likely to receive optimized diabetic care which should lead to a significant reduction in the incidence of kidney disease. It is also possible that diabetic patients who screen positive could
be candidates for prophylactic treatment with Pyridorin™.
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