Epileptic encephalopathies (EEs) are severe, infantile-onset epilepsies characterized by drug-resistant, pleomorphic seizures and early developmental arrest. Malignant migrating partial epilepsy of infancy (MMPEI) is a type of EE. Gain-of-function missense mutations in KCNT1, the gene encoding a sodium-activated potassium channel called Slack, are identified in ~40% of MMPEI patients. There are no approved treatments for MMPEI, but quinidine, a KCNT1 channel modulator, exerts anticonvulsant effects in MMPEI, whereas conventional anticonvulsants routinely fail. These findings suggest that targeting hyperactive KCNT1 channels has therapeutic value. While the anatomical location and neuronal identity in which KCNT1 is expressed is unknown, we hypothesize that MMPEI is an interneuron-driven disease.
|Effective start/end date||1/1/18 → 12/31/20|
- Ann & Robert H. Lurie Children's Hospital of Chicago (#925668-NU)
- Child Neurology Education and Research Foundation (#925668-NU)