The General Hospital Corporation

University of Cincinnati

Gwangju Institute of Science and Technology

Bethphagen Inc.

Nanocor Therapeutics, Inc.

Roger J Hajjar

Federica Del Monte

Evangelia Kranias

Woo Jin Park

Jae Gyun Oh

Anne-Marie Lompr

Larissa Lipskaia

Wolfgang Ch Poller

Henry Fechner

Expression of a phosphatase inhibitor in heart cells can be used to treat cardiac disorders, e.g., heart failure. Decreasing phosphatase activity can improve β-adrenergic responsiveness.

Modulating phosphatase activity in cardiac cells

Expression of a phosphatase inhibitor in heart cells can be used to treat cardiac disorders, e.g., heart failure. Decreasing phosphatase activity can improve &#x3b2;-adrenergic responsiveness.

The present invention relates to decoy peptide or polypeptide consisting of a peptide sequence represented by the following Formula I: X-Ala-X-X-Ile-Glu-X(I). It is noteworthy that the decoy peptide or polypeptide of the present invention significantly elevates phosphorylation levels of PLB by inhibiting PP1-mediated dephosphorylation. In addition, the decoy peptide or polypeptide provides cardio-protective effects by restoring of SERCA2a activity and inotropic effect of enhancing myocardial contractility. The present invention will contribute greatly to the prevention or treatment of diseases associated with PLB.

Decoy peptides inhibiting protein phosphatase 1-medicated dephosphorylation of phospholamban

The present invention relates to decoy peptide or polypeptide consisting of a peptide sequence represented by the following Formula I: X-Ala-X&#x2014;X-Ile-Glu-X(I). It is noteworthy that the decoy peptide or polypeptide of the present invention significantly elevates phosphorylation levels of PLB by inhibiting PP1-mediated dephosphorylation. In addition, the decoy peptide or polypeptide provides cardio-protective effects by restoring of SERCA2a activity and inotropic effect of enhancing myocardial contractility. The present invention will contribute greatly to the prevention or treatment of diseases associated with PLB.

Decoy peptides inhibiting protein phosphatase 1-mediated dephosphorylation of phospholamban

The present invention relates to targeted RNAi for the treatment of heart failure by modulating defective cardiac Cahomeostasis via decreasing expression or activity of phospholamban (PLB) using adeno-associated virus (AAV) transfection of cardiomyocytes. Methods for decreasing ventricular arrhythmias, as well as methods for overall improvement of survival from heart failure in subjects are also disclosed. Further, the present invention provides methods which can be used to diagnose susceptibility to treatment by RNAi, and includes pharmaceutical compositions, kits and vectors including an RNAi sequence.

RNA interference for the treatment of heart failure

Restenosis in a subject can be treated by administering to a tissue, e.g., a blood vessel, of the subject an agent that increases SERCA activity. For example, a stent that is coated with the agent can be introduced into a blood vessel.

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New York, NY, United States of America

Roger J Hajjar