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'Epilepsy in a Dish': Stem Cell Research Reveals Clues to Disease's Origins and May Aid Search for Better Drugs

Created by paustian on Aug 1, 2013, 8:05 AM

 

Scientists at the University of Michigan Medical School have created an exciting new model called “epilepsy in a dish” to study seizure disorders. It works by converting skin cells from patients harboring an epilepsy disorder to stem cells and then to neurons. The patient specific neurons allow for the study of brain cells and brain activity without the need to perform a brain biopsy. The overall goal of this study is to create induced pluripotent stem cells from cells of patients with different epileptic syndromes in order to understand the mechanisms behind the diseases and for drug development.

This technique has been successfully used to study Dravet syndrome. It is a form of severe childhood epilepsy that is characterized by a mutation in the SCN1A gene. This gene encodes the protein Nav 1.1 that regulates sodium channels. Sodium channels are important because they generate action potential, which means they control bodily functions. A mutation in this gene results in the loss of sodium channels in the brain. The neurons developed from the skin cells of children with this rare genetic form of epilepsy responded to this mutation by showing abnormally high levels of sodium current activity as well as bursts of hyperexcitability. Hyperexcitability is an excessive reaction to stimuli that is associated with seizures. Scientists are eager to find out how the loss of the channels leads to hyperexcitability. The nerve cells seem to be overcompensating for the decrease in sodium channels, but it is still a mystery as to how and why the cells are doing this. 

In addition to uncovering the cellular responses in Dravet sydnrome, this model is extremely useful for screening medications. Scientists can test the impact of compounds on the specific neurons. To counteract the effects of the mutation in the SCN1A gene, the researchers are screening for specific compounds to dampen the sodium current and to calm hyperexcitability. This technique has the thrilling potential to give us a better understanding of epileptic syndromes and to create medication for those affected.