Novel Therapies to Block Epileptogenesis in Dravet Syndrome Mice
Sooky Koh, MD, PhD
Dravet Syndrome Foundation 2010 Research Grant Recipient
Dr. Koh is an attending physician at the Neurology and Epilepsy Center at Children’s Memorial Hospital and Assistant Professor of Pediatrics at Northwestern University’s Feinberg School of Medicine. Her interests lie in basic science research on the consequences of seizures on the developing brain, cognitive and neuropsychological effects of anticonvulsant medications and refractory partial onset seizures.
Dr. Koh is an attending physician at the Neurology and Epilepsy Center at Children’s Memorial Hospital and Assistant Professor of Pediatrics at Northwestern University’s Feinberg School of Medicine. Her interests lie in basic science research on the consequences of seizures on the developing brain, cognitive and neuropsychological effects of anticonvulsant medications and refractory partial onset seizures.
Using an animal model of Dravet syndrome, we will characterize the progression of abnormal brain signaling (EEG) and seizure development and determine how inducing multiple seizures affects behavioral and neurologic functioning and future seizure susceptibility. We propose to incorporate several novel strategies to treat epilepsy and increase our understanding of epileptogenesis, the process by which developing brain evolves to produce repeated seizures. We will utilize anti-inflammatory therapy to address the role of brain inflammation in epileptogenesis and seek to answer the question of how repeated seizures may beget more seizures. Early dietary intervention in Dravet syndrome mice can be translated immediately into our clinical practice to alleviate the long term social and cognitive burdens of children newly diagnosed with the syndrome. How gene-environment interaction influences the impact and outcome of seizures will be explored by exposing seizure-prone Dravet syndrome mice to different environments: isolated versus enriched. Molecular mechanisms underlying the long-lasting neuroprotective effects of environmental enrichment will be investigated using gene expression profiling. The promise of our research program is in identifying treatments that minimize the detrimental effects of recurrent seizures, modify disease progression, and prevent chronic epilepsy.