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Please Note: The technology listed below is not available to the public at this time. This technology is in the early stage of research and requires further development before it is ready for the marketplace. The VA is currently in the process of identifying potential companies who may be interested in licensing and/or further developing the technology through Cooperative Research and Development Agreements (CRADA). Through cooperative research initiatives such as these, it is our hope and goal that commercial products will be fully developed and made available to benefit veterans and others.  

VA TECHNOLOGY OPPORTUNITY BRIEF

Quantitation of Atherosclerosis-associated Endothelial Microparticles

(#04-171)

OPPORTUNITY:

The Department of Veterans Affairs (VA) is seeking a commercial partner through a Cooperative Research & Development Agreement (CRADA) to further develop a methodology for the diagnosis and monitoring of atherosclerosis. Areas for collaboration include, but are not limited to, the further development and clinical validation of the subject technology.

BACKGROUND:

Cardiovascular disease, responsible for 16 million deaths annually, is the leading cause of mortality in the industrialized world. The major cause of cardiovascular disease, atherosclerosis, is a progressive condition characterized by the formation of plaques on the inner walls of arteries, the vessels supplying oxygen-rich blood throughout the body. These plaques reduce arterial elasticity and subsequently restrict arterial blood flow, leading to acute ischemia and tissue damage.

The initial event in the pathogenesis of atherosclerosis is the activation or disturbance of the endothelial cells which line the artery and maintain the integrity of the inner arterial wall. This activation is often caused by elevated blood levels of cholesterol and low-density lipoprotein (LDL), two major causes of atherosclerosis. Endothelial cell activation initiates a biological cascade of events responsible for atherosclerotic plaque formation. Upon activation, endothelial cells shed fragments of their plasma membranes, referred to as microparticles, into the bloodstream. Because these circulating endothelial microparticles (EMPs) bear atherosclerosis-specific antigenic markers, EMPs may serve as valid biomarkers for atherosclerosis.

TECHNOLOGY OVERVIEW:

The subject invention provides a precise and reproducible measurement of circulating atherosclerotic-associated endothelial microparticles that is both qualitative and quantitative. The methodology comprises a single platform method, involving application of a patient's plasma sample to fluorescent flow cytometric analysis. Utilization of 'fluorobeads' as enumeration standards and fluorescently-labeled antibodies recognizing distinct EMP surface antigens allow for the accurate and specific quantification of atherosclerotic-associated EMPs. Because this approach requires only a small amount of biological sample, it clearly lends itself to the testing of clinical specimens. Indeed, preliminary studies indicate that the technology is valid for assaying patient samples.

TECHNICAL MERIT:

Conventional methods of diagnosing atherosclerosis are often costly, invasive and highly variable. The subject technology represents a significant improvement over existing methodologies. Utilization of antibodies recognizing only those EMP surface markers unique to atherosclerosis renders the technology qualitative and specific. In contrast to many conventional diagnostic methods, the subject technology provides a systemic enumeration of EMPs, allowing for the detection of atherosclerosis at sites distant from the heart. Utilization of plasma as the biological sample means that the technology also provides an inexpensive and relatively non-invasive method of analysis. Finally, as EMP levels appear to reflect atherosclerotic burden and/or disease activity (e.g. plaque stability), the technology may also be applicable to assessing both the progression of atherosclerosis and treatment response. Thus, the subject invention should dramatically improve both the diagnosis and monitoring of atherosclerosis.

PATENT STATUS:

U.S. patent application was filed April 25, 20005 (11/113,786)
U.S. provisional patent application (60/564,856) was filed April 23, 2004
Federal register notice published November 28, 2005 (Volume 70, Number 227) pg 71378

FOR MORE INFORMATION CONTACT:

Saleem Sheredos
Program Manager
Technology Transfer Program
Veterans Affairs
Office of Research & Development (12TT)
5th Floor
103 South Gay Street
Baltimore, MD 21202
202-380-5080
Fax 410.962.2141
e-mail: saleem.sheredos@va.gov
Last Updated - May 17, 2006