Jacy Wagnon, PhD – Ohio State College of Medicine
$150,000 TWO YEAR RESEARCH AWARD
Many individuals with Dravet syndrome (DS) do not achieve adequate seizure control using available drug treatments. These drugs also do not sufficiently treat other symptoms of DS, including behavioral and cognitive impairments. We analyzed gene expression in a mouse model of DS to identify molecular pathways that may not be functioning correctly in DS. We identified very low expression of a gene, Npas4, that functions to counteract the hyperexcitability in the brain that leads to seizures in DS. We predict that if we restore high expression of this gene in DS mice, hyperexcitability in the brain will be reduced, resulting in fewer seizures and improved behavior and cognition. We propose to test this prediction by delivering the Npas4 gene into the brain of DS mice using a virus. This technique is similar to virus-mediated gene therapy that is currently being used to treat spinal muscular atrophy in children. If this treatment is successful in DS mice, it will indicate that the Npas4 pathway is a good target for development of new treatments for Dravet syndrome.