[Federal Register Volume 61, Number 174 (Friday, September 6, 1996)]
[Notices]
[Page 47132]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-22758]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health


Opportunity for a Cooperative Research and Development Agreement

    National Heart, Lung and Blood Institute (NHLBI); 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, HHS.

ACTION: Notice.

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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.
    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.

    Dated: August 29, 1996.
Sheila Merritt,
Executive Officer, NHLBI.
[FR Doc. 96-22758 Filed 9-5-96; 8:45 am]
BILLING CODE 4140-01-M