New research by Seattle Children’s Research Institute’s Franck Kalume, PhD, and colleagues found a novel genetic approach that could cure Dravet syndrome, a rare and severe form of epilepsy associated with a high rate of sudden, unexpected death. The breakthrough findings are published in the journal Science Translational Medicine.
Dr. Kalume, senior author of the paper and a principal investigator in the research institute’s Norcliffe Foundation Center for Integrative Brain Research, has been researching Dravet syndrome for more than two decades and generated the first preclinical model of the disease. He is considered one of the world’s leading experts in Dravet syndrome research. Over the years, leveraging this disease model, Dr. Kalume and colleagues uncovered deep insights into Dravet syndrome pathophysiology which have served as a critical foundation for the development of a mechanism-based therapy.
Dravet syndrome affects about one in 15,700 children. It usually begins in infancy and causes frequent, prolonged seizures and developmental delays. Current treatment options provide only limited alleviation of symptoms. Patients with Dravet syndrome face a 15% to 20% mortality rate due to sudden, unexpected death, as well as lengthy seizures, accidents and infections.
Mutations in a gene called SCN1A cause most cases of Dravet syndrome. This gene provides instructions to make sodium channel proteins, which play a central role in the generation and propagation of electrical impulses in the brain. In prior work, Dr. Kalume and colleagues showed that Dravet-causing mutations preferentially affect the function of interneurons, with no impact on excitatory neurons. Based on this finding, they predicted that interneurons could serve as a valuable target for a future precision therapy for Dravet syndrome.
