Duke University

Walter J Koch

Robert J Lefkowitz

Jonathan S Stamler

Claude A Piantadosi

Howard A Rockman

Erin J Whalen

Carmelo A Milano

Per-Otto Hagen

Louis M Luttrell

Shahab A Akhter

Howard A Royman

The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (&#x3b2;-AR). &#x3b2;-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a &#x3b2;-AR transgene, a &#x3b2;-ARK transgene, or a &#x3b2;-ARK inhibitor transgene.

Use of exogenous &#x3b2;-adrenergic receptor and &#x3b2;-adrenergic receptor kinase gene constructs to enhance myocardial function

Desensitization of receptors that control disease is prevented by inhibiting G-protein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event or on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis.

Preventing desensitization of receptors

The present invention relates, in general, to vascular smooth muscle proliferation and, in particular, to a method of inhibiting arterial and venous smooth muscle proliferation resulting, for example, from arterial injury or vein grafting. The invention also relates to an expression construct encoding a G&bgr;&ggr; inhibitor suitable for use in such a method.

Method of inhibiting smooth muscle cell proliferation

The present invention relates, in general, to myocardial hypertrophy and, in particular, to agents that inhibit cardiac Gq-coupled receptor signaling and to methods of inhibiting myocardial hypertrophy using same.

Intracellular inhibitors of Gq protein signaling

The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (&bgr;-AR). &bgr;-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a &bgr;-AR transgene, a &bgr;-ARK transgene, or a &bgr;-ARK inhibitor transgene.

Use of exogenous &bgr;-adrenergic receptor and &bgr;-adrenergic receptor kinase gene constructs to enhance myocardial function

The present invention relates, in general, to vascular smooth muscle proliferation and, in particular, to a method of inhibiting arterial and venous smooth muscle proliferation resulting, for example, from arterial injury or vein grafting. The invention also relates to an expression construct encoding a G.beta..gamma. inhibitor suitable for use in such a method.

Growing community of inventors

Durham, NC, United States of America

Walter J Koch