Authors: Stephanie Neys, Kristina Kooiker, Amy Martinson, Darren Hwee, James Hartman, Anne N Murphy, Bradley Morgan, Jennifer Davis, Fady Malik, Farid Moussavi-Harami
Published: 2023-10-13
DOI: 10.1161/res.133.suppl_1.ec.04
Source: Full article
Genetic dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. However, most treatments do not address the underlying contractile deficit caused by the disease. In an effort to create more targeted DCM therapeutics, novel small molecule drugs known as sarcomeric modulators have been of recent interest. In a recent study, a cardiac troponin activator was shown to improve cardiac muscle contractility without adversely affecting energetics or diastolic function. Here, we aim to elucidate the mechanism by which the cardiac troponin activator CK-3827358 (CK-358) is able to recover contractile function in a mouse model of DCM with a mutation at residue 61 of cardiac troponin C (cTnC I61Q). We measured steady state force and