AGY THERAPEUTICS IDENTIFIES CATHEPSIN B AS IMPORTANT IN MEDIATING NERVE CELL DEATH IN CELLULAR MODEL OF ALZHEIMER’S DISEASE
-- Identification of Key Neurotoxic Factor Published in the Journal of Biological Chemistry --

SOUTH SAN FRANCISCO, Calif. – Feb. 10, 2004 – AGY Therapeutics Inc. today announced the publication of studies that identified cathepsin B, an important regulatory protein, as having a crucial role in mediating inflammation-induced nerve cell death, a condition associated with chronic neurodegenerative conditions such as Alzheimer’s Disease (AD). The publication appears in the latest edition of the peer-reviewed Journal of Biological Chemistry.

The paper entitled “Identification of cathepsin B as a mediator of neuronal death induced by Aß-activated microglial cells using a functional genomics approach” outlines studies carried out by AGY scientists using the company’s powerful ImAGYne™ technology platform. Detailed genome-wide expression analysis in cultured mouse microglial cells identified 554 genes that were transcriptionally upregulated in response to the Aß peptide stimulus. Several of these genes were then selected for further investigation. Functional analysis of this subset using RNA interference technology to specifically inhibit expression of individual genes showed that inhibition of cathepsin B significantly decreased the toxic effect on primary neurons, suggesting that this protein is important to the microglia-induced neurotoxic effect.

“Cathepsin B has been implicated as a key mediator in a number of pathological conditions including Alzheimer's disease, tumor invasion and cell death,” said Karoly Nikolich, Ph.D., founder and chief scientific officer of AGY Therapeutics. “This study pinpoints this important protein as a major mediator of the neurotoxic effects of activated microglial-induced neuronal cell death and therefore potentially as a key contributor to progressive neurodegeneration and cognitive decline associated with Alzheimer’s.”

“The rapid identification and characterization of such targets is a prerequisite to accelerating the development of treatments that allow for early therapeutic intervention to stall or perhaps even halt the progress of neurological deterioration associated with this disease,” said Cynthia J. Ladd, AGY’s president and CEO. “Despite incredible progress in the development of novel therapeutics for a wide range of human conditions such as heart disease and even cancer, our knowledge of many diseases of the brain and central nervous system remains rudimentary. Our ImAGYne technology platform provides us with a leadership position in this specialized and technically demanding area.”

About Alzheimer’s Disease
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of dementia among the elderly, currently affecting 4.5 million people. The incidence is expected to rise as the population ages. The causes of AD are still unknown, and there is no cure.

AD affects the parts of the brain that control thought, memory and language. It is characterized by abnormal clumps and tangled bundles of fibers in the brain, known as senile plaques and neurofibrillary tangles. Activated microglia are found to be intimately associated with senile plaques and may play a central role in mediating chronic inflammatory conditions in AD.

About ImAGYne
AGY Therapeutics' proprietary ImAGYne™ platform defines the intra- and extra-cellular signaling pathways that underlie the pathological progression of central nervous system (CNS) diseases, so novel, high-quality targets can be carefully selected and functionally validated with the most valuable targets advanced into drug discovery and development. To date, AGY Therapeutics has identified and characterized a number of promising drug targets to treat or diagnose CNS diseases and has identified potential lead compounds.

About AGY Therapeutics
AGY Therapeutics, Inc., a privately held biotechnology company, is dedicated to discovering and developing novel treatments for CNS diseases, including stroke, depression, cognitive and mental diseases and brain tumors.

For additional information contact:
Kristin Nash
WeissCom Partners
415-302-7951
info@agyinc.com
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