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Researchers use stem cells to determine new therapies for severe childhood epilepsy

Tuesday, December 6, 2011 01:52 PM
A U-M team of researchers investigating the fundamental cause of Dravet syndrome, a severe childhood epilepsy, have reprogrammed fibroblasts, a type of skin cell, from Dravet patients and generated patient-specific neurons- which could help determine new therapies or better medications for the syndrome.
 
Jack M. Parent, M.D., working in collaboration with Lori Isom, Ph.D., and Miriam Meisler, found that these patient-derived neurons showed increased excitability, abnormal neuronal behavior that can produce seizures.
 
Parent, who is also co-director of U-M's EEG/Epilepsy Program, and his team obtained fibroblasts from both Dravet patients and unaffected controls and reprogrammed the cells to induced pluripotent stem cells (iPSCs) by gene transfer.
 
Forebrain-like neurons were generated from the iPSCs and studied for their
electro-physical properties. The Dravet-derived neurons displayed a lower
threshold for electrical activity, more repetitive firing, 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 prove a valuable tool to evaluate potential new medications for Dravet syndrome and potentially other developmental epilepsies," added Parent.
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