Researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have identified a new molecular mechanism driving hypertrophic cardiomyopathy, the most common inherited heart disease. A study published in Nature Cardiovascular Research confirms that the targeted therapy mavacamten remains effective across various genetic mutations, potentially expanding treatment options for the estimated 95,230 patients living with the condition in Spain.
How does the newly identified mutation affect the heart?
Hypertrophic cardiomyopathy often stems from mutations in the MYBPC3 gene, which encodes cardiac myosin binding protein C. While many mutations lead to a drop in protein levels, the newly studied R502W variant functions differently. According to Laura Sen Martín, first author of the study, this mutation alters the protein’s ability to interact with other cardiac proteins rather than simply reducing its quantity.
The research team created a mouse model carrying the R502W variant to observe these effects. They found that the mutation specifically reduces the ability of cardiac myosin binding protein C to interact with myosin, the molecular motor responsible for heart contraction. This discovery provides a clearer understanding of the molecular chain reaction that causes the heart muscle to thicken and contract with excessive, potentially dangerous force.
Hypertrophic cardiomyopathy is a leading cause of sudden cardiac death in young people and athletes. It affects roughly 1 in every 250 to 500 people, according to data from the Spanish Heart Foundation and the CIBERCV.
Is mavacamten effective for all genetic variants?
The study suggests that mavacamten’s clinical utility is broader than previously understood. By testing the drug on both the R502W mouse model and models with a complete loss of cMyBP C, researchers observed that the drug successfully halted pathological heart muscle remodeling in both groups.
Dr. Jorge Alegre Cebollada, head of the CNIC Molecular Mechanics of the Cardiovascular System Group, notes that while the drug is transforming treatment, patient response has historically been variable. The findings indicate that this inconsistency is likely not due to the specific type of mutation a patient carries. In laboratory-grown human cardiac tissue, the drug consistently reduced excessive contractile force, suggesting a consistent therapeutic benefit across different molecular origins of the disease.
What does this mean for future patient care?
Because mavacamten modulates myosin activity directly, it addresses the “hypercontractility” that characterizes the disease regardless of the underlying genetic trigger. Researchers now aim to determine if early administration of the drug can improve therapeutic outcomes, a question that remains unresolved in the clinical setting.
When discussing treatment options, patients should consult their cardiologists about whether their specific genetic profile makes them candidates for targeted therapies like mavacamten.
Frequently Asked Questions
What is the primary cause of hypertrophic cardiomyopathy?
It is an inherited condition caused by mutations in genes that encode sarcomere proteins, the molecular machinery of the heart. The MYBPC3 gene is one of the most frequently involved.
How does mavacamten work?
Mavacamten acts on myosin to modulate its activity. By doing so, it reduces the excessive force of heart muscle contractions, which helps prevent the abnormal thickening and rhythm disruptions associated with the disease.
Can this research help athletes at risk?
Because the disease is a leading cause of sudden cardiac death in athletes, identifying these molecular mechanisms early is vital. The new mouse model provides a tool for testing future targeted therapies that could eventually be used to intervene before life-threatening symptoms develop.
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