Tuberous sclerosis complex (TSC) is an orphan, genetic disorder associated with brain malformations resulting in life-long epilepsy in 85-90% of patients. The incidence is high with 1/6,000 new births, and seizures occur early in life and result in several debilitating comorbidities. The standard of care, brain surgery and everolimus treatment, is inadequate due to limited efficacy and severe side-effects. There is a critical need for new options to treat seizures and its comorbidities. Recent work from my lab identified three molecular targets to treat seizures in TSC. We propose to pursue gene therapy (RNAi and AAV) and small molecule treatment against two of the identified targets.