Cardiac Therapy: cardiac hypertrophy therapy with biologics
RhoGEF12 inhibition for the prevention and therapy of cardiac hypertrophy, -fibrosis, and -failure
Heart failure is a disabling and potentially deadly condition which affects 1-2% of adults in developed countries; in the population above 65 years the incidence increases to 6–10% (McMurray and Pfeffer 2005). Possible causes include increased pressure or volume load, as found in arterial hypertension or valve disease. To compensate reduced cardiac output, structural cardiac remodeling is initiated, including cardiac hypertrophy and fibrosis. This initially compensatory reaction may counterproductively reinforce the clinical signs of heart failure.
So far, the mechanisms underlying the transition from hypertrophy to heart failure are not well defined and thus therapeutic options are limited.
Scientists from the Max Planck Institute for Heart and Lung Research have identified a key molecule responsible for the development of cardiac hypertrophy, namely the RhoGEF12 protein (or LARG). Inactivation of RhoGEF12-dependent RhoA activation protects the heart from hypertrophy development, cardiomyocyte apoptosis, fibrosis, and the development of chronic heart failure. Mice with inducible, cardiomyocyte-specific inactivation of the RhoGEF12 (cmc-GEF12-KO) were protected from cardiac hypertrophy and fibrosis in two models of pressure overload, and their cardiac output function was improved compared to wt mice. Importantly, also in mice with preexisting hypertrophy, induction of RhoGEF12 deficiency protects from cardiac decompensation, resulting in significantly increased longterm survival.
We are looking for a collaboration- and/or licensing partner who is interested in this approach and eager to develop these scientific achievements into a marketable good.