Gene correction in an attempt to cure heart disease

The primary goal of REPAIR is to investigate and optimize the therapeutic effects of advanced and promising gene therapies to address the underlying genetic cause of a severe kind of heart disease, known as hypertrophic cardiomyopathy. To this end, we have brought together an interdisciplinary consortium that combines expertise in experimental models for heart disease and gene therapies with excellent knowledge of drug improvement and patient populations.

Genetic heart muscle diseases (cardiomyopathies) often affect young individuals for which there are currently few available medications. In the Netherlands, an important form of genetic heart muscle disease is linked to mutations in the Myosin Binding Protein C3 (MYBPC3) gene. MYBPC3 mutations lead to hypertrophic cardiomyopathy, characterized by excessive muscle growth of the heart chamber and an increased risk of sudden death as a result. Current treatment focuses mainly on palliative care, with implantable defibrillators or heart transplants being seen as a last resort. However, recent advances in gene therapy now allow us to eliminate the underlying cause of genetic diseases by correcting the disease driving mutation. This technology could lead to the development of a curative therapy for the first time. However, to achieve a safe and effective treatment for heart disease, the activity, specificity and delivery to the heart of this approach still need to be improved.

If successful, we will develop this technology as a new, innovative therapy for carriers of this disease-driving mutation. With this, REPAIR may have a major impact on the quality of life for this patient population, but also provides hope and insights for the development of gene therapies for other genetic diseases.