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La Jolla Pharma Discovers Molecule That Produces Positive Results

http://www.thetsector.com/displayarticle6400.html

December 2, 2003
The Sector

La Jolla Pharmaceutical Company today announced the discovery of novel, orally-active small molecules for the treatment of autoimmune diseases and acute and chronic inflammatory disorders.

Company scientists have generated highly selective inhibitors of SSAO (semicarbazide-sensitive amine oxidase), an enzyme that has been implicated in inflammatory responses in many tissues and organs. Preclinical studies in animal models of multiple sclerosis, rheumatoid arthritis and acute inflammation have shown that treatment with the Company's inhibitors both maintained function and reduced disease activity compared with placebo treatment.

"We have discovered several families of potent, orally-active small molecule inhibitors of SSAO that reduce disease in a variety of animal models," said Matthew Linnik, Executive Vice President of Research and Chief Scientific Officer of La Jolla Pharmaceutical Company. "The impact of these lead compounds on animal models of multiple sclerosis and rheumatoid arthritis was similar to that of methotrexate, a widely used anti-inflammatory agent. We are excited about the potential to provide a novel approach to treating a number of debilitating diseases."

SSAO, also known as vascular adhesion protein-1 or VAP-1, was recently discovered to be a dual-function molecule with enzymatic and adhesion activities. SSAO contributes to the adhesion of white blood cells to endothelial cells and is greatly amplified in inflamed blood vessels. The enzyme also contributes to the production of molecules that exacerbate inflammation. Increases in the levels of plasma or membrane-associated SSAO have been reported for many inflammation-associated diseases including rheumatoid arthritis, inflammatory bowel disease, diabetes, atherosclerosis, and chronic heart failure. In preclinical studies conducted by Company scientists, SSAO inhibitors blocked both the enzymatic and adhesion functions of SSAO and were shown in animal models to be potent inhibitors of disease activity. These results will be presented at the 2nd International Inflammatory & Immune Diseases World Summit on March 8-10, 2004 in Baltimore, MD.
 

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