MicroRNA-mediated modification of Dravet syndrome

This project touches on two of the DSF 2019 priority areas, including (i) enhancing understanding of the genetic and molecular mechanisms that lead to Dravet syndrome, and (ii) encouraging development of novel therapies to prevent onset or halt progression of Dravet syndrome. First, we will investigate a potential miRNA-mediated feedback loop between seizure activity and Nav1.1 expression. This could provide insight into a potential molecular mechanism underlying disease progression, and may suggest a potential target for RNA-mediated therapeutic intervention. In parallel, we test whether an ASO strategy targeting seizure-mediated miRNAs or their binding site in Scn1a 3’UTR has therapeutic benefit in the Scn1a+/- Dravet mouse model. If successful, this will provide pilot data for development of an RNA-mediated ASO strategy targeting the SCN1A 3’UTR, which differs from the strategies currently in development (e.g. poison exon targeting by Stoke Therapeutics).