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Cycle adenosine monophosphate-incompetent adenylyl cyclase and compositions and methods for treating heart failure and increasing cardiac function

A heart failure, heart function technology, applied in biochemical equipment and methods, drug combinations, enzymes, etc., can solve problems such as heart damage, discomfort, treatment of heart failure, and increased mortality

Inactive Publication Date: 2016-03-30
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these drugs often increase mortality
Current thinking assumes that drugs and proteins that increase intracellular cAMP levels are harmful to the failing heart and therefore unsuitable for the treatment of heart failure

Method used

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  • Cycle adenosine monophosphate-incompetent adenylyl cyclase and compositions and methods for treating heart failure and increasing cardiac function
  • Cycle adenosine monophosphate-incompetent adenylyl cyclase and compositions and methods for treating heart failure and increasing cardiac function
  • Cycle adenosine monophosphate-incompetent adenylyl cyclase and compositions and methods for treating heart failure and increasing cardiac function

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0220] Example 1: Delivery of ACs unable to produce cAMP increases cardiac function

[0221] This example demonstrates the effectiveness of an exemplary embodiment of the invention: delivery of cAMP-incapable AC to cardiomyocytes for the treatment of heart failure. In this study, we asked whether AC mutant molecules that reduce LVcAMP production would have beneficial effects on left ventricular (LV) function through their effects on Ca2+ disposal alone.

[0222] So many clinical trials of positive inotropes have failed that it is now self-evident that agents that increase cAMP are harmful to failing hearts. An alternative strategy is to alter myocardial Ca using agents that do not affect cAMP 2+ disposition or myofilament to Ca 2+ the response to. Although left ventricular (LV) function is tightly linked to adenylate cyclase (AC) activity, the beneficial effects of AC may not be related to cAMP but instead arise from the response to Ca 2+ The role of disposal.

[0223] ...

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Abstract

The invention provides methods for treating, ameliorating or protecting (preventing) an individual or a patient having or at risk of having heart disease or heart failure, or decreased cardiac function, comprising: providing a cyclic adenosine monophosphate-incompetent (cAMP-incompetent) adenylyl cyclase type 6 (AC6) protein or polypeptide (also called "an AC6mut"), or an AC6mut -encoding nucleic acid or a gene operatively linked to a transcriptional regulatory sequence.

Description

[0001] related application [0002] This Patent Cooperation Treaty (PCT) international application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 61 / 832,759, filed June 7, 2013. The above application is expressly incorporated herein by reference in its entirety for all purposes. technical field [0003] The present invention relates generally to cellular and molecular biology, gene therapy, and medicine; and more particularly to the administration of adenylate cyclase type 6 (AC6) proteins or polypeptides that are incapable of producing cyclic AMP (cAMP-incapable) proteins or polypeptides (also known as "AC6mut") or a nucleic acid sequence encoding AC6mut Composition methods of treating a subject suffering from or at risk of heart failure or heart disease. Background technique [0004] Adenylate cyclase, a transmembrane protein in cardiomyocytes and other cells, is a key effector molecule that transduces p-adrenergic signaling thr...

Claims

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Application Information

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IPC IPC(8): C12N9/88
CPCC12N9/88C12Y406/01001A61P43/00A61P9/00A61P9/04A61K38/51
Inventor H·K·哈蒙德高美华
Owner RGT UNIV OF CALIFORNIA
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