Project 461343

Dravet Syndrome (DS) is a devastating and sometimes fatal neurodevelopmental disorder. Its symptoms include severe epilepsy as well as neurological and developmental disorders. Roughly 80% of affected individuals carry a mutation in a gene called SCN1A, while others carry a mutation in the gene SCN1B. Both genes code for cell surface proteins that regulate the flow of sodium into nerve cells: SCN1A encodes a protein that forms a channel through which sodium flows, and SCN1B encodes a protein that regulates the channel's function. The flow of sodium through the channel helps to conduct the electrical pulses required for nerve cell function and the communication between the brain and muscles and tissues. Because of the disease-associated mutations in these sodium channels, the electrical conduction ability of the affected nerve cells is impaired, thereby causing epileptic seizures and other DS symptoms. The goal of this project is to develop a novel gene therapy for the treatment of DS. We will test our ability to deliver a healthy copy of a sodium channel gene to affected nerve cells and study the efficacy of our gene therapy using two different mouse models of DS disease. The techniques that we develop may be applicable to other genetic diseases as well, such as other types of epilepsy and schizophrenia. It is our hope that the therapies we design will one day be used in humans to cure this devasting disease and establish new gene therapy techniques to help Canadians live longer, more healthy lives.