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.