The Epilepsy Foundation is pleased to announce its first annual Targeted Research Initiative for Severe Symptomatic Epilepsies grant program. This program seeks to better understand, diagnose, identify co morbidities, and treat these rare but devastating epilepsy syndromes. The catastrophic epilepsies of childhood commonly include Othara's syndrome, severe myoclonic epilepsy in infancy (Dravet), infantile spasm, progressive myoclonic epilepsies, Lennox-Gastaut syndrome, Doose syndrome, Sturge-Weber syndrome, Rasmussen encephalitis and, in later childhood, Landau-Kleffner syndrome (LKS) and continuous spike and wave in slow-wave sleep (CSWSS).


Hee Jung Chung, Ph.D.
The Board of Trustees of the University of Illinois at Urbana-Champaign, Urbana, IL
Mechanisms of KCNQ2 mutations associated with Epileptic Encephalopathy

Neurons generate electrical signals called action potentials in their morphologically distinct processes named axons. KCNQ channels concentrated at the axonal surface allow potassium ions to move from inside to outside of the neurons. Such current through these channels prevents "repetitive firing of action potentials", which is a hallmark of excessive neuronal activity leading to seizures. Mutations in KCNQ2 subunit protein of these channels are recently found in patients with epileptic encephalopathy, severe epilepsies of childhood characterized by drug-resistant seizures and psychomotor impairment. Some of these mutations are clustered in the cytoplasmic tail of KCNQ2 subunit, which is important for surface expression or opening and closing of the channels. The proposed research will investigate whether these mutations reduce potassium current and/or axonal localization of KCNQ channels, leading to excessive action potential firing. Two small molecule compounds will also be explored for their ability to enhance the channel surface expression. These studies should provide insights into the pathogenesis of this disease and facilitate the development of novel therapy that could correct the loss of channel surface expression.