University of Colorado

Arca Biopharma, Inc.

University Technology Corporation

Other

The University of Texas System

Michael R Bristow

Stephen Bryant Liggett

Jonathan D Port

Eric N Olson

Timothy McKinsey

Leslie A Leinwand

J David Port

Christopher Dufton

Wayne Minobe

Carlin Long

Koichi Nakao

Robert L Edwards

Carmen Sucharov

Koichiro Kinugawa

Dobromir Slavov

Matthew Taylor

James E Harwood

Jonathan David Port

The current methods and compositions relate to treatment of atrial fibrillation with bucindolol in patients, including patients with heart failure, after being determined to be homozygous Arg389 in the &#x3b2;adrenergic receptor gene.

Methods and compositions involving bucindolol for the treatment of atrial fibrillation

Disclosed is bucindolol substantially free of its R-stereoisomer. Also disclosed are pharmaceutical compositions that include bucindolol substantially free of its R-stereoisomer or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Also disclosed are methods of treating a patient that involve administering to the patient a therapeutically effective amount of a composition of the present invention.

Methods and compositions involving (S)-bucindolol

Embodiments of the invention are directed to identifying or treating a patient that would benefit from phosphodiesterase inhibitor therapy.

Polymorphisms in the PDE3A gene

Disclosed is bucindolol substantially free of its R-stereoisomer. Also disclosed are pharmaceutical compositions that include bucindolol substantially free of its R-stereoisomer or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Also disclosed are methods of treating a patient that involve administering to the patient a therapeutically effective amount of a composition of the present invention. Formula (I). 

The present invention concerns the use of methods for evaluating bucindolol treatment for a patient, particularly one with heart failure. It concerns methods for determining whether to administer or prescribe bucindolol to a patient based on whether the patient is homozygous for the Arg 389 polymorphism in the &#x3b2;1-adrenergic receptor (AR).

Methods for treatment with bucindolol based on genetic targeting

The invention provides a method of treating myocardial failure in a human. The method comprises administering an effective amount of transgene encoding &#x3b1;-MHC that directly causes an increase in the quantity of &#x3b1;-MHC in the myocardial tissue of the heart.

Diagnosis and treatment of myocardial failure

The present invention provides methods of diagnosing myocardial failure in a human. The methods comprise obtaining a sample of myocardial tissue from a ventricle of the heart. In one embodiment, the expression of &#x3b1;-myosin heavy chain, &#x3b2;-myosin heavy chain, or both, are quantitated and their expression levels compared to that seen normal human ventricular myocardial tissues. In another embodiment, the expression of &#x3b1;1-thyroid hormone receptor, &#x3b1;2-thyroid hormone receptor, a &#x3b1;1-thyroid hormone receptor+&#x3b2;1-thyroid hormone receptor, or combinations thereof, are quantitated, and their expression levels compared to that seen normal human ventricular myocardial tissues. Therapeutic interventions based on altering the expression of the aforementioned genes also are provide.

The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.

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Greenwood Village, CO, United States of America

Michael R Bristow