Oxidation Resistant form of Apolipoprotein A-I
Introduction High density lipoprotein (HDL) protects against atherosclerosis by removing cholesterol from cells of the artery wall. Apolipoprotein A-I (apoA-I), which accounts for ~70% of the total protein in HDL, promotes cholesterol and phospholipid efflux largely by an active transport process. There has been increasing interest in the development of apoA-I to treat or prevent cardiovascular disease. However, oxidation severely impairs the ability of apoA-1 to promote cholesterol efflux. Moreover, in human atherosclerotic lesions and the blood of subjects with established coronary artery disease apoA-I is chlorinated, suggesting that apoA-I oxidation might promote atherogenesis. Researchers at the University of Washington have engineered mutations in apoA-1 that are resistant to oxidation and might be especially anti-atherogenic in vivo. Technology description The cardioprotective effects of HDL and apoA-I may be lost when HDL is oxidatively modified in vivo. UW researchers have identified specific sites in apoA-1 that, when oxidized, cause it to lose its cardioprotective effects. Additionally, they have engineered mutations in apoA-1 that have been shown to render it resistant to this oxidative inactivation. This “oxidation resistant” apoA-1 could be a novel treatment for the prevention of cardiovascular disease. Moreover, recent studies suggest that HDL is a potent antiinflammatory agent, raising the possibility that "oxidation resistant" apoA-I could be useful in wide range of inflammatory diseases as well. Business opportunity According to the WHO, cardiovascular and atherosclerotic diseases represent the leading cause of mortality in developed nations. Drugs currently available are effective for preventing the development plaque, but are less effective at actually decreasing the existing plaque burden. HDL-targeted therapies are emerging as an important new class of pharmaceuticals, which for the first time may reduce existing plaque deposits by elevating HDL and reverse cholesterol transport. The therapeutic potential of apoA-I has been recently assessed in patients with acute coronary syndromes, using a recombinant form of a naturally occurring variant of apoA-I (called apoA-I Milano). An oxidation resistant form of apoA-I, used alone or in conjunction with other forms of apoA-1, could represent an improved treatment for the prevention and reversal of cardiovascular disease. Intellectual property position The University has applied for patent protection to secure the rights to this technology. Related Publication(s)
J Biol Chem. 2006 Apr 7;281(14):9001-4. Epub 2006 Feb 22. Curr Opin Cardiol. 2006 Jul;21(4):322-8).
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