A team of researchers from the Institute for Basic Science (IBS) said they identified a new pathogenesis and treatment strategy for autistic patients with epilepsy lacking the Ank2 gene.

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication, and repetitive behaviors. It is often accompanied by several co-morbidities, and about 30 percent of patients have epilepsy. Additionally, people with epilepsy are about eight times more likely to be diagnosed with autism than the general population. This suggests that the two disorders may share similar genetic variations.

The prevalence of ASD continues to rise worldwide but the pathogenesis and treatment remain poorly understood.

Accordingly, the study led by Professor Kim Eun-joon of the IBS Center for Synaptic Brain Dysfunctions showed how epilepsy develops in a mouse model lacking the gene ANK2, which is a genetic risk factor for autism and epilepsy. 

The researchers identified increased excitability of cortical neurons in Ank2-deficient mice, which may be because Ank2 deficiency causes cortical neurons to lose their initial segment of the axon.

An axon is a long, fiber-like segment of a nerve cell that functions to transmit signals to other nerve cells. Its initial segment is responsible for regulating neuronal excitability.

In nerve cells, potassium channels are proteins present in the cell membrane and serve as channels for the movement of potassium ions and regulate the electrical excitability of the nerve cell.

The researchers discovered that mice without this gene developed epileptic seizures and subsequently died in adolescence from seizures.

Based on this pathogenesis, the researchers used retigabine, an anti-epileptic medicine, to enhance potassium channel function in Ank2 knockout mice. As a result, they were able to restore neuronal excitability to normal levels and reduce death-induced seizures, suggesting that activation of potassium channels may be effective in treating epilepsy caused by Ank2 defects.

"We found that mutations in the Ank2 gene increased the excitability of neurons, leading to symptoms of autism-related epilepsy," said Professor Kim, who led the study. "This study sheds light on the mechanisms and treatment possibilities of autism-related epilepsy."

The results were published on June 15 in the international journal, Nature Communications.