Hypertrophic cardiomyopathy (HCM) is a common genetic heart condition affecting 1 in 200–500 people worldwide. It is characterized by structural abnormalities, including enlarged heart muscle cells, which compromise heart function and increase the risk of heart failure, stroke, and potentially fatal arrhythmias.

A rare and severe form of HCM, linked to mutations in the TRIM63 gene, is the focus of our study. TRIM63 is crucial for breaking down and removing damaged proteins in heart muscle cells. Mutations in this gene lead to the accumulation of these proteins, causing cell damage, abnormal heart growth, and life-threatening complications such as heart failure and arrhythmias.

To address this, we aim to develop an innovative therapy using Proteolysis-Targeting Chimeras (PROTACs). These molecules employ the cell’s natural protein degradation system to target and remove the harmful protein buildup caused by TRIM63 deficiency. Using a cutting-edge heart-on-chip model—engineered miniaturized human heart tissues grown from patient cells—we will study the disease mechanisms and guide the design of safe and effective PROTAC therapeutics.

Our research aims to provide a first-of-its-kind therapy for TRIM63-related HCM. If successful, this approach could improve heart health, reduce life-threatening complications, and serve as a model for treating other genetic heart diseases, offering hope to patients who currently lack effective treatments.