Novel Approach Reveals Potential Mechanism Underlying Dravet Syndrome
December 3, 2011
Scientists investigating the cause of Dravet syndrome, a severe childhood epilepsy, have reprogrammed fibroblasts, a type of skin cell, from Dravet patients and generated patient-specific neurons. Further study revealed that these patient-derived neurons showed increased excitability and abnormal neuronal behavior can produce seizures. This novel approach toward unraveling the pathophysiological mechanism behind Dravet syndrome was reported today at the American Epilepsy Society's 65th annual meeting.
Jack M. Parent and colleagues at the University of Michigan obtained fibroblasts from both Dravet patients and unaffected controls. The cells were reprogrammed to induce pluripotent stem cells (iPSCs) by gene transfer. Forebrain-like neurons were generated from the iPSCs and studied from their electro-physical properties. The Dravet-derived neurons displayed a lower threshold for electrical activity, more repetitive fire and increased firing frequency than control neurons.
"These findings indicate that patient-specific mutant Dravet cells can be reprogrammed to successfully model an epileptic-like phenotype with in vitro seizure-like activity," Parent says. "Besides providing new insight into disease pathogenesis, this approach using patient-specific cells should have a valuable tool to screen novel therapies or to evaluate potential new medications for Dravet syndrome and potentially other developmental epilepsies." This approach should also have broader applications in screening new treatments for other neurological disorders.
Dravet syndrome, also called severe myoclonic epilepsy of infancy (SMEI), is a rare genetic disorder with typical onset in the first year of life.