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| METABOLEX ANNOUNCES PUBLICATION OF PRECLINICAL
STUDY IN DIABETES |
First Study to Implicate Certain Enzymes in Destruction of Islet Cells in Animal Model of Type 2 Diabetes |
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Hayward, Calif.,
(August 31, 2005): Metabolex, Inc. today announced the publication of preclinical data showing for the first time that matrix metalloproteinases (MMPs) are involved in islet destruction – a hallmark of type 2 diabetes – and may contribute to the worsening of the disease. MMPs are enzymes that, when highly activated, contribute to pathologies such as arthritis, cardiovascular disease and cancer. The study also found that an investigational compound that inhibits MMPs can prevent type 2 diabetes in an animal model. The study, entitled “Matrix Metalloproteinases Contribute to Insulin Insufficiency in Zucker Diabetic Fatty Rats,” was conducted by researchers at Metabolex in partnership with scientists at Pfizer. Study results appear in the September 1 issue of Diabetes, a peer-reviewed journal published by the American Diabetes Association.
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| “These findings represent an important advance in our understanding of the cause of type 2 diabetes at the molecular level. Because human islets also express high levels of MMPs, this study suggests that therapeutic agents that specifically inhibit MMPs may be able to preserve islet function in the face of insulin resistance and may slow the progression to diabetes. This would represent an entirely new way of preventing the destruction of islets,” said Jeffrey D. Johnson, Ph.D., co-author of the study and Principal Scientist at Metabolex. “As the incidence of type 2 diabetes is skyrocketing with the aging of the population and the increasing incidence of obesity, it will be important to explore MMP inhibitors to see if they can preserve islet function and positively impact type 2 diabetes.” |
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Type 2 diabetes has two primary characteristics – progressive insulin resistance (in which the pancreas makes insulin but muscle and fat cells do not respond to it properly, resulting in high blood glucose levels) and failure of islets, clusters of cells in the pancreas that contain insulin-secreting cells known as β-cells. When insulin resistance occurs, often because of obesity, the islets try to compensate by secreting more insulin, but, in many individuals, eventually diabetes results.
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In an effort to understand the molecular changes associated with pancreatic β-cell dysfunction that occur during the onset of type 2 diabetes, the investigators conducted a comprehensive survey of all of the genes expressed in islets in an animal model of type 2 diabetes. Using customized microarrays, the researchers examined the genes expressed in the islets during the onset of diabetes. Of the 12,000 genes studied, the most striking change was a very large increase in the expression of MMPs, enzymes that when elevated have been implicated in several pathological conditions, including cancer, fibrosis, arthritis and atherosclerosis. To further evaluate the role of MMPs in the destruction of islets, the investigators treated the animals with an inhibitor of MMPs and found that it prevented type 2 diabetes in the animals. |
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“The publication of this scientific paper illustrates our expertise in understanding the underlying biology and genetic basis of diabetes,” said Harold E. Van Wart, Ph.D., president and CEO of Metabolex. “We are committed to discovering and developing novel therapeutics to treat and prevent diabetes and have built a rich pipeline of product candidates and drug discovery targets, including metaglidasen, a next-generation insulin sensitizer in phase 2 clinical trials, MBX-2044, a follow-on compound that has completed a Phase 1 clinical trial, and several validated drug targets for obesity and diabetes with our research partner Astellas Pharma Inc.” |
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| About Metabolex |
Metabolex is a privately held biotechnology company dedicated to the discovery and development of novel therapeutics to transform the treatment of diabetes and related metabolic disorders. Metabolex has drawn on its deep understanding of diabetes to create the largest database of genes involved in diabetes and to build a rich pipeline of product candidates and drug discovery targets. The company’s clinical program is focused on developing next-generation insulin sensitizers that lower blood glucose without the serious safety and tolerability issues associated with currently marketed products. |
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| For additional information about Metabolex and its development pipeline, visit www.metabolex.com. |
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