Sarcomere protein modulation: The new frontier in cardiovascular medicine and beyond

Cristina Morelli, Gessica Ingrasciotta, Daniel Jacoby, Ahmad Masri, Iacopo Olivotto

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalEuropean Journal of Internal Medicine
StatePublished - Aug 2022


  • Cardiomyopathies
  • Heart failure
  • Neuromuscular diseases, therapeutics
  • Sarcomeres

ASJC Scopus subject areas

  • Internal Medicine


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