Novel inotropic/lusitropic biologics against decompensated chronic heart failure

The objectives of this proposal are the preclinical development of a cardiac-targeted peptide drug with inotropic and lusitropic effects for the short-term intravenous treatment of decompensated chronic heart failure (CHF) and its clinical translation into a first-in-human clinical trial. The life-threatening complication of the clinical syndrome presents a significant unmet medical need given its high mortality and severe adverse effects of clinical drugs to reconstitute cardiac performance. The proposed therapeutic innovation seeks to exploit a novel regulatory principle to improve cardiac contraction and relaxation by the molecular factor S100A1 and utilizes cell-permeable peptide technology that is derived from the molecule’s C-terminal domain. The translational research project originates from comprehensive preclinical data showing the ability of S100A1ct peptide for a reversible short-term improvement and protection of cardiac performance in vivo and in vitro. In its funded first developmental module, the project seeks to define the therapeutically effective dose-range of S100A1ct in clinically relevant large animal disease models as well as demonstration of toxicological and immunological safety to conclude regulatory steps on ultimate GMP/GLP pre-clinical and clinical development.