Precision treatment of pediatric genetic epilepsy: EEG biomarkers and circuit mechanisms

Epilepsy, the tendency of the brain to have spontaneous seizures, affects 1% of all children, costing $4 billion dollars per year in the United States. With increasing availability of genetic testing, there is unprecedented opportunity to diagnose the root cause of epilepsy and develop new, more effective treatments to directly address underlying biological causes (i.e., precision treatment). However, for the vast majority of children with epilepsy, precision treatment is not yet available; treatments remain empirical, symptomatic and ineffective in >30%. 

We identified a drug that is already approved in the US for the treatment of depression, that restores normal genetic function, cognition and social behavior in mice modeling a severe form of childhood-onset epilepsy, intellectual disability and autism, SYNGAP1. We now propose studies to determine whether this drug also reduces seizures and brain circuit abnormalities in SYNGAP1 mice.

We will use machine learning approaches to identify a disease signature for SYNGAP1 that can be used to measure disease severity and treatment response with a common test, the electroencephalogram (EEG). At the conclusion of this work, we will submit an IND application (to conduct a clinical trial) to the US Food and Drug Administration.

This research will serve as a prototype for future translational projects leveraging the joint expertise of both the neuroscience research community and clinicians working in the pediatric genetic epilepsy clinic at Stanford, to develop precision therapies for children with severe epilepsy.