Lead Inventors: Xian-Cheng Jiang, Ph.D. and Alan R. Tall, Ph.D. Problem or Unmet Need: Cardiovascular disease has been the leading causes of illness in the U.S. for many decades. Atherosclerosis alone affects over 4.5 million people. Characterized by...

Lead Inventors: Xian-Cheng Jiang, Ph.D. and Alan R. Tall, Ph.D. Problem or Unmet Need: Cardiovascular disease has been the leading causes of illness in the U.S. for many decades. Atherosclerosis alone affects over 4.5 million people. Characterized by high plasma cholesterol levels, triglycerides, and various lipoproteins, new therapeutics that are able to reduce these components are in great demand. Furthermore, dyslipidemia, such as occurs in familial combined hyperlipidemia, diabetes and obesity, is also an important disease treated through the administration of therapeutics that reduce blood cholesterol and lipid levels. Alternatives to the currently available treatments would provide greater flexibility for physicians in addressing these diseases. Details of the Invention: The increased production of apolipoprotein B-containing lipoproteins is thought to be a major cause of accelerated atherosclerosis and the principal defect in those with familial combined hyperlipidemia as well as comprise an important component of the dyslipidemia of diabetes and obesity. This invention demonstrates that the reduction in the activity of plasma phospholipid transfer protein (PLTP) results in a reduction of apolipoprotein B-containing lipoproteins and triglycerides. Indeed, human apolipoprotein B transgenic mice lacking PLTP showed a 50% reduction of total cholesterol and atherosclerotic lesion area, due to reduced hepatic secretion of apoB lipoproteins. Furthermore, inhibitors of PLTP showed a strong anti-atherosclerosis potential in rabbits. This invention covers the treatment of dyslipidemia and cardiovascular disease by the administration of a compound effective in decreasing PLTP activity as well as a method of identifying chemical compounds that decrease PLTP activity. Applications: • PLTP could serve as a target for the treatment of atherosclerosis and dyslipidemia • Furthermore, this invention also provides a method for the identification of chemical compounds that decrease PLTP activity Advantages: • PLTP represents a novel target for the treatment of dyslipidemic and atherosclerotic diseases Patent Status: Issued patent US 6,953,671 B2 Publications: 1) Liu R, Iqbal J, Yeang C, Wang DQ, Hussain MM, Jiang XC. Phospholipid transfer protein-deficient mice absorb less cholesterol. Arterioscler Thromb Vasc Biol. 2007 Sep;27(9):2014-21. 2) Liu R, Hojjati MR, Devlin CM, Hansen IH, Jiang XC. Macrophage phospholipid transfer protein deficiency and ApoE secretion: impact on mouse plasma cholesterol levels and atherosclerosis. Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):190-6 3) Jiang XC, Li Z, Liu R, Yang XP, Pan M, Lagrost L, Fisher EA, Williams KJ. Phospholipid transfer protein deficiency impairs apolipoprotein-B secretion from hepatocytes by stimulating a proteolytic pathway through a relative deficiency of vitamin E and an increase in intracellular oxidants. J Biol Chem. 2005 May 6;280(18):18336-40. 4) Schlitt A, Bickel C, Thumma P, Blankenberg S, Rupprecht HJ, Meyer J, Jiang XC. High plasma phospholipid transfer protein levels as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1857-62. 5) Yang XP, Yan D, Qiao C, Liu RJ, Chen JG, Li J, Schneider M, Lagrost L, Xiao X, Jiang XC. Increased atherosclerotic lesions in apoE mice with plasma phospholipid transfer protein overexpression. Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1601-7. 6) Jiang XC. The effect of phospholipid transfer protein on lipoprotein metabolism and atherosclerosis. Front Biosci. 2002 Jul 1;7:d1634-41. 7) Jiang XC, Qin S, Qiao C, Kawano K, Lin M, Skold A, Xiao X, Tall AR. Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat Med. 2001 Jul;7(7):847-52. Websites: http://www.downstate.edu/anatomy/faculty/jiang.html http://cpmcnet.columbia.edu/dept/medicine/tallcv.html Licensing Status: Available for Licensing and Sponsored Research Support

Pat. Title: PLASMA PHOSPHOLIPID TRANSFER PROTEIN (PLTP) DEFICIENCY REPRESENTS AN ANTI-ATHEROGENIC STATE AND PLTP INHIBITOOR HAS ANTI-ATHEROSCLEROSIS ACTION PLASMA PHOSPHOLIPID TRANSFER PROTEIN (PLTP) DEFICIENCY REPRESENTS AN ANTI-ATHEROGENIC STATE AND PLTP INHIBITOR HAS ANTI-ATHEROSCLEROSIS ACTION PLASMA PHOSPHOLIPID TRANSFER PROTEIN (PLTP) DEFICIENCY REPRESENTS AN ANTI-ATHEROGENIC STATE AND PLTP INHIBITOR HAS ANTI-ATHEROSCLEROSIS ACTION

Publication #: 02-0142280-A1 1373555 WO 02/068450

App. #: 09/792,448 2713684.5 PCT/US02/05694

Patent #: 6953671

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