CSR 9

iPSC and Mouse Neurocardiac Models

Specific Aims and Tasks

This core aims to determine whether heart rhythm disturbances are a cause of Sudden Unexplained Death in Epilepsy (SUDEP) in Dravet Syndrome, a severe childhood epilepsy with a high risk of SUDEP. The proposed studies involve a unique combination of experiments using patient-derived heart cells and neurons, mouse models, and patient electrocardiogram data obtained before, during and after seizures. Progress in these Aims will complement and synergize with the other projects in this proposal to not only uncover SUDEP mechanisms in Dravet Syndrome that will likely be applicable to other severe epilepsies, but also to provide advances in identifying biomarkers to define at-risk patients. Utilize iPSC-derived cardiac myocytes and autonomic neurons as well as mouse models to determine whether heart rhythm disturbances are a cause of SUDEP in Dravet Syndrome, a severe childhood epilepsy with a high risk of SUDEP

• Focus on SCN1A and SCN1B mutations and investigation of their effect on cardiac and autonomic neuron excitability

Principal Investigators

• Jack Parent, MD
• Lori L. Isom, PhD
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