Allosteric modulators of force production: towards precision medicine for different classes of heart diseases

Hypertrophic and dilated cardiomyopathies are highly prevalent cardiac diseases. They result from distinct single-point mutations in sarcomeric proteins that lead to muscle dysfunction. Most of the current treatments for end-stage cardiomyopathies such as heart transplantation or implantable-cardioverter are highly invasive. Recently, a new approach using small-molecules able to modulate myosin force production has been proposed to treat cardiac disease. Some of these small molecules such as the activator Omecamtiv mecarbil (OM) and the inhibitor Mavacamten (Mava) are currently in advanced clinical trials.