Congestive Heart Failure (CHF) is defined as the inability of the heart to pump blood forward at a sufficient rate to meet the metabolic demands of the body. Heart failure results in a decrease in cardiac output, activating several endogenous neurohormonal systems. In failing human hearts, there is a severe refractoriness to ß-adrenergic stimulation in which the ß-adrenergic receptor-cAMP system is severely down regulated by excessive exposure to the high levels of cathecholamines, and this refractoriness causes significantly reduced cardiac contractility. The sarcoplasmic reticulum (SR) plays an integral role in cardiac contractility by the coordination of the movement of cytosolic Ca2+ during each cycle of cardiac contraction and relaxation. Activity of the cardiac SR Ca2+ ATPase (SERCA2a) is the rate-determining factor of Ca2+ reuptake into the SR, and SERCA2 activity is itself regulated by Phospholamban (PLN). The PLN-SERCA2 interaction is a regulatory control point in mediating cardiac contractility and progression of dilated cardiomyopathy.
Winter 2008 Lecture Series:
"Technology; Change and Challenge.
Dr. Krisztina Zsebo, CEO
Celladon's product MYDICAR® targets SERCA2a, resulting in increased cardiac contractility and cardiac output, and has shown beneficial results in preclinical studies in reversing the morbidity and mortality of CHF. Celladon is currently conducting clinical trials in NYHA Class III/IV heart failure patients.
Congestive Heart Failure (CHF) is defined as the inability of the heart to pump blood forward at a sufficient rate to meet the metabolic demands of the body. Heart failure results in a decrease in cardiac output, activating several endogenous neurohormonal systems. In failing human hearts, there is a severe refractoriness to ß-adrenergic stimulation in which the ß-adrenergic receptor-cAMP system is severely down regulated by excessive exposure to the high levels of cathecholamines, and this refractoriness causes significantly reduced cardiac contractility. The sarcoplasmic reticulum (SR) plays an integral role in cardiac contractility by the coordination of the movement of cytosolic Ca2+ during each cycle of cardiac contraction and relaxation. Activity of the cardiac SR Ca2+ ATPase (SERCA2a) is the rate-determining factor of Ca2+ reuptake into the SR, and SERCA2 activity is itself regulated by Phospholamban (PLN). The PLN-SERCA2 interaction is a regulatory control point in mediating cardiac contractility and progression of dilated cardiomyopathy.
