Researchers create stem cell model to identify potential targeted epilepsy treatment

In a new study published in the scientific journal Brain, researchers at Children’s Hospital of Philadelphia have used human pluripotent stem cells (iPSC) to create a model for epilepsy and other neuronal diseases connected to mutations in the gene SCN3A. The model can provide increased understanding of the behind why mutations in SCN3A lead to neurological disease could enable development of novel therapeutic approaches for multiple neurological disorders that today lack adequate treatment and that are linked to high childhood mortality.

Epilepsy is a neurological disease characterized by recurrent seizures that are caused by abnormal, excessive, purposeless and synchronized neuronal discharges. Today, there are approximately 50 million people living with epilepsy around the world and the disease is responsible for more than 125,000 deaths annually. One of the causes behind epilepsy is mutations in the in the gene SCN3A, which is also linked to a host of other conditions collectively known as SCN3A-related neurodevelopment disorders.

The gene SCN3A encodes for the Nav1.3 subunit of voltage gated sodium channels, proteins that are highly expressed in the central nervous system and that play lay fundamental roles in initiating and propagating action potentials in neurons. However, mutations in SCN3A can disrupt the ion channel function, leading to severe epilepsy as well as structural malformation in the development of the cerebral cortex.

In their study, the researchers at Children’s Hospital of Philadelphia have used modified iPSCs to create a model containing the disease-related variant of the ion channel (iNeuron). With this method, the researchers found that the modified iNeurons expressing the variant had increased slowly-inactivating sodium ion currents that led to abnormal neuron firing patterns.

To test the feasibility of the Nav1.3 subunit as a therapeutic target, the researchers used BioPen to transiently expose the iNeurons to pharmacological agents. Their results showed that treatments with Nav1.3-selctive blockers could restore neuronal activity to normal, confirming the model's usefulness as a screening platform.

We at Fluicell congratulate the scientist at Children’s Hospital of Philadelphia on their achievement and are happy that they have chosen to use Fluicell’s precision technology in their important research.

Read the full article, recently published in the scientific journal Brain.

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