Over the past decade, the constant progress in science and technologies has provided innovative
drug molecules that address specific disease mechanisms thus opening the era of drugs targeting the underlying pathophysiology of the disease. In this scenario, a new paradigm of modulation has emerged, following the development of small molecules capable of interfering with sarcomere
contractile proteins. Potential applications include heart muscle disease and various forms of
heart failure, although promising targets also include conditions affecting the skeletal muscle, such as degenerative
neuromuscular diseases. In cardiac patients, a
cardiac myosin stimulator,
omecamtiv mecarbil, has shown efficacy in
heart failure with reduced systolic function, lowering
heart failure related events or cardiovascular death, while two inhibitors,
mavacamten and aficamten, in randomized trials targeting
hypertrophic cardiomyopathy, have been shown to reduce hypercontractility and
left ventricular outflow obstruction improving functional capacity. Based on years of intensive basic and translational research, these agents are the prototypes of active pipelines promising to deliver an array of molecules in the near future. We here review the available evidence and future perspectives of
myosin modulation in cardiovascular medicine.