Do anti-epileptic drugs prevent sudden cardiac death in people with CPVT?

Catecholaminergic polymorphic ventricular tachycardia: Investigating the relationships between RyR2 dysfunction in the brain and sudden cardiac death

CPVT1 is a rare inherited disease that affects children and young adults. It causes disturbances to the heart rhythm (arrhythmias) and can lead to sudden cardiac death. CPVT1 is caused by a genetic mutation of a protein called ryanodine receptor 2 (RyR2) that is highly abundant in the heart and brain. It is usually assumed that abnormal activity of RyR2 in the heart is responsible for sudden cardiac death in CPVT1. However, recent studies suggest that there may be a link between abnormal brain activity and sudden cardiac death. People with CPVT1 often suffer from seizures before any heart symptoms appear, and are therefore diagnosed with epilepsy. Furthermore, two anti-epileptic drugs are believed to act on ryanodine receptors. In this project, Dr Charalampos Sigalas and a team of scientists at the University of Oxford aim to determine if anti-epileptic drugs are beneficial for people with CPVT1. The researchers will assess the direct effects of anti-epileptic drugs on the activity of RyR2 in the hearts and brains of healthy mice and mice with a genetic mutation linked to CPVT1 in humans. They will also test if drugs currently used to treat CPVT1 can reduce epileptic activity in brains with dysfunctional RyR2. This research will help us understand why sudden cardiac death happens in young people with CPVT1 and could lead to improved treatments e.g. by repurposing anti-epileptic drugs to treat CPVT1.