KCNH2 Pilot Drug Rescue
This study focuses on KCNH2, a gene that plays a critical role in controlling the heart's electrical rhythm. Variants in KCNH2 can disrupt the function of the potassium channel it encodes, leading to Long QT Syndrome type 2 (LQTS2), a condition that increases the risk of dangerous arrhythmias and sudden cardiac death. While some patients with KCNH2 variants experience severe symptoms, others remain unaffected, and there are currently limited therapeutic options that directly target the underlying channel dysfunction.The goal of this pilot project is to test whether certain small molecules or drugs can "rescue" the function of defective KCNH2 channels in HEK cells. By studying how these cells respond to candidate drugs, we can determine whether channel activity can be restored, potentially normalizing electrical signaling in the heart.This work is highly relevant because it directly bridges genetic discoveries to potential therapies. If successful, the pilot study will provide proof-of-concept that precision medicine approaches - matching therapies to specific genetic variants - are feasible for arrhythmia disorders. Beyond immediate therapeutic insights, the project will generate valuable data on which KCNH2 variants are most amenable to drug rescue, creating a foundation for larger studies and informing clinical trial design. Ultimately, this research could open new treatment avenues for patients living with LQTS2 and related rhythm conditions, where sudden cardiac events remain a devastating clinical challenge.