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.

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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.