Lecithin Cholesterol Acyltransferase (LCAT) for the Treatment of Atherosclerosis and LCAT Deficiency
Published in the Federal Register on Friday, September 6, 1996
(Volume 61, Number 174), page 47132 [61 FR 47132]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Heart, Lung and Blood Institute
Opportunity for a Cooperative Research and Development Agreement (CRADA) for the development of different therapeutic modalities to raise plasma concentrations of the enzyme lecithin cholesterol acyltransferase (LCAT) for the treatment of atherosclerosis and LCAT deficiency.
AGENCY: National Institutes of Health, PHS, DHHS
ACTION: Notice
SUMMARY: In humans, the development of atherosclerosis is positively and inversely correlated with the plasma levels of low density lipoproteins (LDL) and high density lipoproteins (HDL) respectively. LCAT, the major enzyme involved in the esterification of free cholesterol present in circulating plasma lipoproteins, is a major determinant of plasma HDL concentrations. Recent studies have established that transgenic rabbits overexpressing human LCAT have 6-7 fold higher plasma HDL levels than control, non-transgenic siblings. In addition, LCAT transgenic rabbits have reduced plasma concentrations of the atherogenic LDL and apoB-containing lipoproteins. This lipoprotein phenotype characterized by elevated plasma HDL and reduced LDL levels leads to marked protection against the development of diet-induced atherosclerosis in LCAT transgenic rabbits compared to control animals.
The NHLBI of the NIH is seeking capability statements from parties interested in entering into a CRADA on the development of different therapeutic modalities to raise plasma concentrations of the enzyme lecithin cholesterol acyltransferase (LCAT) for the treatment of atherosclerosis and LCAT deficiency. This project is with the Molecular Disease Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. The goals are to use the respective strengths of both parties to achieve one or more of the following:
1) Evaluate the feasibility of gene therapy utilizing the LCAT gene and suitable vectors as a treatment approach for the prevention of atherosclerosis in animal models as well as patients with premature cardiovascular disease; and,
2) Evaluate the use of gene therapy to correct LCAT deficiency in LCAT knockout mice models systems and patients with LCAT deficiency; and,
3) Develop and evaluate the anti-atherogenic properties of pharmacological agents that raise plasma concentrations of LCAT.
It is anticipated that the commercial collaborator(s) will participate in ongoing studies on one or both of the research projects involving (1) the transfer of the human LCAT gene in animal models and patients with atherosclerosis or LCAT deficiency and (2) the development of pharmacologic agents that will increase plasma concentrations of LCAT. It is highly desirable that the collaborator have the resources to provide new effective vectors for the long term in vivo expression of the LCAT gene. The collaborator may also be expected to contribute financial support under this CRADA for supplies and personnel to support these projects.
ADDRESS: CRADA capability statements should be submitted to Ms. Lili Portilla, Technology Transfer Specialist, National Heart, Lung, and Blood Institute, Technology Transfer and Commercialization Team, 31 Center Drive MSC 2490, Bldg. 31/ Room 1B32, Bethesda, Maryland 20892-2490; Phone: (301) 402-5579; Fax: (301) 594-3080. Capability statements must be received by the NHLBI on or before October 7, 1996.
The NHLBI has applied for patents claiming this core technology. Non-exclusive and/or exclusive licenses for these patents covering core aspects of this project are available to interested parties. Licensing inquiries regarding this technology should be referred to Ms. Carol Lavrich, Licensing Specialist, NIH Office of Technology Transfer, 6011 Executive Blvd., Suite 325, Rockville, Maryland, 20852-3804; Phone: (301) 496-7735, Ext.287; Fax: (301) 402-0220.