Norimichi Higurashi, Taku Uchida, Shinichi Hirose and Hideyuki Okano
Dravet syndrome is devastating infantile-onset epilepsy, often accompanied by severe intellectual disabilities, hyperactive behavior, autistic traits, and ataxia. The discovery in 2001 of theSCN1Amutation as a primary cause of this syndrome has accelerated our understanding of the pathophysiological processes underlying Dravet syndrome. SCN1A encodes the α-subunit of the voltage-gated sodium channel, NaV1.1. Recent studies using genetically modified mouse models have indicated that haplo insufficiency of NaV1.1inGABAergic inhibitory inter neurons in the forebrain may be involved in the seizure susceptibility, fever sensitivity of seizures, premature death, and autistic traits characteristic of Dravet syndrome. More recently, human cellular models of Dravet syndrome have been established
using patient-derived induced pluripotent stem cells (iPSCs) from three groups including ours. By taking advantage of these human disease models, functional vulnerabilities in GABAergic neurons have been revealed. Here, we review recent advances in Dravet syndrome research, particularly focusing on the development of iPSC models, and their future directions.
