Epilepsy afflicts approximately 750,000 children in the United States and ~45,000 children suffer severe forms beginning in infancy. Early infantile epileptic encephalopathies (EIEE) are a devastating form of epilepsy characterized by global developmental delays, motor and speech deficits, autism, and intractable seizures with a high risk of sudden death (SUDEP). Unfortunately, conventional and newer anti-epileptic drugs control the seizures of only a small percentage of children with EIEE. Mutations in a large set of genes have been implicated in the etiology of EIEE, several of which are in voltage gated ion channels.
In 2012, the Hammer lab discovered the first mutation (SCN8A-N1768D) in the sodium channel SCN8A (Nav1.6) in a patient with early onset intractable seizures, developmental delay, and SUDEP. There are now over 300 patients known worldwide with SCN8A-related epilepsy with encephalopathy, and thousands more with related sodium ion channelopathies.
In our lab, we employ a knock-in mouse carrying the N1768D (D/+) mutation to test therapeutic interventions in an animal model that is more representative of human epilepsy than current chemical-induced animal models. In collaboration with Dr. Lalitha Madhavan, we have established a human pluripotent stem cell (iPSC) line with the N1768D variant to complement pathophysiological studies in the mouse, and to enhance therapeutic potential.