In the July 2nd issue of the journal Annals of Neurology, Drs. Liu and colleagues representing a large group from numerous institutions present a fascinating and important research study addressing the cause of Dravet syndrome. Dravet syndrome is believed to be due to a genetic mutation in SCN1A that encodes for a voltage-gated sodium channel. Loss of this function, however, has been difficult to reconcile without understanding of how nerve cells send signals.
The investigators used pluripotent stem cells (iPSC) to generate patient specific neurons. They created four brain-like pyramidal and bipolar-shaped neurons from two Dravet syndrome subjects and three human controls by the use of stem cell reprogramming of fibroblasts.
The Dravet syndrome and the control stem cell derived neurons were compared using specialized electrical recordings to understand how these nerve cells fire and potentially create seizures.
The researchers found the following:
The Dravet syndrome neurons have increased sodium currents in both the bipolar and pyramidal-shaped neurons.
Consistent with the increased sodium currents, both types of these neurons show spontaneous bursting and other evidence of increased excitability that one would expect in such a syndrome.
The findings showed that epilepsy patient-specific stem cell derived neurons are useful for modeling epileptic-like hyperactivity.
The authors concluded that their findings reveal an unrecognized cell-autonomous epilepsy mechanism that underlies Dravet syndrome. Stem cell models of patient neurons may represent a new way to screen new treatments for epilepsy.
Stem cell models of patient neurons may represent a new way to screen new treatments for epilepsy.