Beta-3 Adrenergic Receptor Agonists Reduce Cardiac Hypertrophy and Heart Failure
Abstract (Set) This invention is based on the discovery of a novel role for beta-3 adrenergic receptors (B3AR) in the control of cardiac hypertrophy when the heart is under physical stress. The precise role of B3AR in the heart has not been previously elucidated. In general, beta-1 and -2 adrenergic receptors are activated when the heart is under stress (?fight or flight response?); however, activation of B3ARs have an opposite effect. B3AR are increased in human heart failure as a protective mechanism, but it is at a level insufficient to prevent disease. We recently observed that mice lacking B3AR develop cardiac hypertrophy, a precursor to congestive heart failure and an independent predictor of cardiac death. When mice lacking B3AR are subjected to a model of pressure-overload by transverse aortic banding (TAC), they have increased mortality and much worse hypertrophy (among survivors). Our new invention is a method for increasing stimulation of B3AR using pharmacologic B3AR-specific agonists to reverse or prevent cardiac hypertrophy and treat all forms of heart disease related to cardiac hypertrophy, such as non-systolic heart failure. Description (Set) Beta-3 adrenergic receptor signaling plays a suppressive role in the pathogenesis of cardiac pressure-overload by enhancing eNOS uncoupling. Selective stimulation of these receptors may provide a novel approach to reducing pathologic remodeling in the hypertrophied and/or failing heart. Proposed Use (Set) Cardiac hypertrophy is a predictor of heart failure (both systolic and non-systolic) and an independent predictor of cardiac mortality. To date there have been no pharmacologic agents that were known specifically to treat this condition. This therapeutic method using of B3AR agonists can be comercialized as a treatment for cardiac hypertrophy and non-systolic heart failure.Heart failure is one of the leading causes of death.Inventor(s): Barouch, Lili ,Kass, David,Moens, An
Type of Offer: Licensing
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