FOR IMMEDIATE RELEASE

Report in PNAS on role of Nephrin, the kidney
filter protein
-- Studies identify nephrin as a key target for therapeutic strategies to improve kidney function --

Research Triangle Park, N.C., July 6 /PRNewswire/ -- BioStratum Incorporated announced today the publication in the journal "Proceedings of the National Academy of Sciences" (volume 96, pages 7962-7967) of the paper entitled "Nephrin is specifically located at the slit diaphragm of glomerular podocytes." The work was completed in the laboratory of one of BioStratum's founding scientists, Dr. Karl Tryggvason of the Karolinska Institute, Stockholm, Sweden.

In this paper, nephrin is found at the "slit diaphragm," also referred to as the "slit membrane," an important structure in the kidney's filtration barrier. Until now, very little has been known about how the kidney filters blood. Nephrin appears to form a "zipper-like" filtration structure that functions both as a key structural motif which organizes and maintains the integrity of the filtration barrier as well as a porous filtration structure that allows the liquid portion of the blood to pass but not plasma proteins.

A break-down in the kidney's ability to filter proteins is a common occurrence in most kidney diseases, and results in proteinurea (protein in the urine). Proteinuria is not only
a consequence of kidney disease, but also is generally regarded as a major contributing factor to the development of end-stage renal disease, a condition often associated with diabetes and one that requires renal placement therapy (transplantation, dialysis). Nephrin's key role in
the kidney's filtration barrier suggests that treatments
that increase the production of this protein or restore its function are likely to improve kidney function by restoring the kidney's ability to filter proteins. BioStratum owns intellectual property rights to nephrin and new treatments based on modulating nephrin function.

"This advance holds great promise for the development
of treatments for a broad range of kidney diseases, which
are an enormous medical problem in this country," said
Dr. Archie Prestayko, President and CEO of BioStratum. "In fact, the U.S. spends $12 billion annually treating kidney disease."

The present work elegantly depicts the location of nephrin at the slit membrane using nephrin specific antibodies that can be detected by electron microscopes. The structural domains of the nephrin molecule suggest a membrane bound receptor that self-associates with a nephrin molecule on a neighboring podocyte cell surface, thus forming a zipper-like connection between the cells, i.e. the slit membrane.

The nephrin gene was originally identified using genetic linkage analysis on patients with a rare disease called congenital nephrotic syndrome, which is a disease characterized by massive proteinuria. The discovery of the nephrin gene was reported last year by Dr. Tryggvason's group in a paper published in Molecular Cell (March 1998, Volume 1, pages 575-582).

"The absence of a functioning nephrin protein has a profound effect on the kidney's filtration barrier.
Therapeutic strategies which increase the production
of a functional nephrin protein are a promising approach
to restore kidney function and arrest proteinuria," said
Dr. Tryggvason. "In support of this strategy are results obtained in our laboratory and other laboratories that demonstrate a correlation between nephrin function and proteinuria in both genetic and acquired kidney diseases."

BioStratum is pursuing several approaches to increase nephrin production including the identification of small molecule drugs that specifically increase nephrin expression, and the application of BioStratum's
proprietary Glomerular Gene Transfer Technology.
In this approach, a nephrin gene will be transferred
into the kidney in order to express a functional nephrin protein to restore the kidney's filtration function.
Dr. Tryggvason's group has developed this technology
and demonstrated the transfer of functional genes into
the kidneys of pigs.

BioStratum Incorporated is a privately held company developing proprietary therapeutics based on recent scientific advances in basal lamina and related technologies. The company's therapeutics are directed against novel basal lamina extracellular targets involved in degenerative and invasive disease processes fundamental to kidney disease, diabetes and cancer. The company has also developed methods for the production of recombinant basal lamina proteins for use in wound repair and advanced tissue regeneration protocols.

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