FOR IMMEDIATE RELEASE
BioStratum Reports Promising Advances for Treatment of Progressive
-- Nephrotic syndrome gene identified. Codes for key protein in kidney
-- Drug candidate Pyridorin™ prevents development of diabetic kidney disease
Research Triangle Park, N.C., March 20, 1998 -- BioStratum Incorporated
today announced that a research team led by its scientific cofounder has
identified the gene and its corresponding protein responsible for the
kidney disease congenital nephrotic syndrome. More over the results from
this discovery provide a promising target for
the development of treatments for proteinuria, a common and serious complication
of many kidney diseases.
In related news, the Company also reported that its drug candidate Pyridorin™
prevented the development of kidney disease in a preclinical animal model
The research team headed by BioStratum cofounder professor Karl Tryggvason
at the Karolinska Institute
in Stockholm, Sweden, has succeeded in identifying
the mutant gene responsible for congenital nephrotic syndrome, a human
kidney disorder characterized by massive leakage of blood proteins into
the urine, termed medically as proteinuria.
Congenital nephrotic syndrome is usually fatal in early childhood, and
the only available treatment is kidney transplantation. The results provide
for the immediate
DNA-based diagnosis of congenital nephrotic syndrome and the identification
of individuals that are carriers for
this disease. Researchers from Finland, Sweden and the U.S. contributed
to the study titled, "Positionally Cloned Gene for a Novel Glomerular
Protein-Nephrin-Is Mutated in Congenital Nephrotic Syndrome" that was
published today in Molecular Cell (Volume 1, #4).
The identified gene encodes for a new protein named nephrin. Preliminary
work indicates that nephrin is found
at the surface of cells that comprise the blood filtration barrier of
the kidney. Its apparent function is to maintain
the integrity of the glomerular epithelials cells, and for their anchorage
to components of the glomerular basement membrane involved in blood filtration.
"This discovery provides new fundamental knowledge about the kidney's
filtration barrier and, furthermore, provides a new target for the development
of treatments for proteinuria. While congenital nephrotic syndrome is
relatively rare, proteinuria is a major complication in numerous diseases
affecting the kidney, and a principal complication of the many disorders
that can lead to end stage renal disease, including diabetic nephropathy,"
said Professor Tryggvason.
On the drug development front, a BioStratum sponsored study conducted
by Dr. John Baynes at the University
of South Carolina, is providing promising results on BioStratum's drug
candidate Pyridorin™, a member
of a new class of post-Amadori inhibitors of diabetic complications. The
study demonstrates its efficacy
in preventing the development of proteinuria and other
diabetic kidney disease pathologies in a rat model of diabetes. The model
used, the streptozotocin (STZ)
animal model, is widely accepted as one of the best available to test
the efficacy of drugs for diabetic kidney disease. Pyridorin™ inhibits
the formation of advanced glycation end-products (AGEs), which are thought
be a major contributing factor in the development of
diabetic kidney disease. It specifically blocks conversion
of a key intermediate of AGE formation. Pyridorin™ also exhibits a very
favorable toxicity profile in animal studies.
BioStratum is a privately held company developing proprietary therapeutics
based on recent scientific advances in basal lamina and related technologies.
The company's drug candidates 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.