Development and Assessment of an Engineered Cardiac Tissue for Treating Dilated Cardiomyopathy

Abstract Non ischemic dilated cardiomyopathyDCMis a progressive disease that causes global left ventricularLVand right ventricularRVdysfunction leading to heart failure and deathThe prognosis for non ischemic DCM is poorwith data suggesting close toyear mortality without a heart transplantThe prevalence iscasespopulation year with a high incidence in patients andltyears oldThe treatment includes aggressive pharmacologic therapychronic resynchronization therapyRCTCardioNEMStype monitoring and ventricular assist devicesNone of these treatments addresses the primary pathology of DCMloss of functioning cardiomyocytesUltimatelythe only effective treatment for DCM is heart transplanthoweverthe number of donor organs is limited and has been stagnant for decadesA new treatment that replaces lost cardiomyocytes and improves cardiovascular function would provide a much needed therapy for patients with DCMAvery Therapeutics proposes a new treatment for non ischemic DCM using a bioengineered cardiac tissueMyCardiathat can generate new myocardium and reverse maladaptive LV remodeling in animal models of ischemic chronic heart failureCHFSpecificallywe have shown that MyCardia generates new cardiac myocytesreverses left ventricularLVmaladaptive remodelingreduces LV volumesimproves LV systolic and diastolic functionelectrically enhances conduction in the native myocardium with no electrical dyssynchronyno arrhythmiasand activates endogenous growth factor secretion that increases myocardial blood flowWe believe that we can achieve these same benefits in patients with non ischemic DCMresulting in function and quality of life improvementsThese positive changes should translate into benefitting patients with less shortness of breath and increases in functional capacity with improved exercise toleranceWe propose to develop a therapy for both dogs and humans Project NarrativeDilated cardiomyopathy results in a poor prognosis andyear mortality without heart transplantAvery Therapeutics is developing a new treatment for dilated cardiomyopathyan allogeniec tissue engineered graftwhich provides electrical and structural benefit over a large area of the heartWe intend to finalize our quality manualrelease criteriaand pre clinical requirements before submitting an application to the FDA to test in a genetically defined canine dilated cardiomyopathy population