Researchers Discover $3 Epilepsy Drug Alleviates Autism-Associated Behavior

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An inexpensive epilepsy drug can “switch off” autism, according to a new peer-reviewed study published Tuesday in the journal Molecular Psychiatry.

Led by Dr. Moritz Mall from the Hector Institute for Translational Brain Research in Germany, researchers in the study found that the drug lamotrigine, which is sold under the brand name Lamictal, among others, was able to curb behavioral issues associated with autism spectrum disorder (ASD).

First approved for use in the United States in 1994, lamotrigine is an anti-seizure, anti-epilepsy drug and is also used to stabilize mood in bipolar disorder.

It costs as little as $3 for 30 100-mg tablets and, according to a paper found in the National Library of Medicine, works by inhibiting “voltage-gated sodium channels, stabilizing presynaptic neuronal membranes” and “inhibiting presynaptic glutamate and aspartate release.”

In simple terms, it slows down the electrical signals that prompt seizures, making them stop.

Researchers in their study analyzed the role of the protein MYT1L, which is found in every neuron (brain cell) and plays a key role in deciding which genes are active in the cell and which ones are not during the development and growth of the brain.

Mutations of MYT1L have been linked to cognitive disability, autism spectrum disorder, and other neurological diseases, as well as obesity, but scientists do not know the cause of the alterations.

Study Method

To better understand the impact of MYT1L on autism symptoms, researchers in the latest study examined the effects of MYT1L deficiency in human neurons and mice.

Specifically, the researchers genetically created MYT1L mutations in both mice and human nerve cells that had been engineered from reprogrammed stem cells in the laboratory.

They found that mutations caused a reduction in MYT1L protein length and that mice lacking the protein had brain abnormalities, including a thinner cerebral cortex.

The mice also exhibited multiple signs of autism including social deficits and hyperactivity, suggesting that MYT1L deficiency could be a cause of ASD.

“We also found that gene expression changes in MYT1L-mutant mouse brains directly resembled those observed in ASD patient brains, demonstrating that MYT1L deficiency can lead to ASD-associated transcriptional profiles,” the authors wrote.

Additionally, the researchers found that MYT1L deficiency prompted an increase in the amount of sodium released from neurons from sodium channels, called SCN5A. Excess sodium release is also known as electrophysiological hyperactivation.

Electrophysiological hyperactivation is a common symptom of autism and other neurological disorders.

Autism Treatments

When MYT1L-deficient nerve cells were treated with lamotrigine, a sodium channel blocker, their electrophysiological activity returned to normal.

“In order to find a potential therapeutic intervention, we decided to test whether lamotrigine, a sodium channel blocker and FDA-approved anti-epileptic drug, could rescue MYT1L deficiency-induced phenotypes,” the authors wrote. “Indeed, acute application of lamotrigine normalized electrophysiological network hyperactivity of both human and mouse MYT1L-deficient neurons toward control levels.”

ASD is described by the U.S. Centers for Disease Control and Prevention as a “developmental disability that can cause significant social, communication, and behavioral challenges.”

Roughly one in 44 children in the United States has been diagnosed with ASD and it is four times more common among boys than girls. Current treatments include behavioral, developmental, educational, and pharmacological approaches.

“Overall, we present the first evidence that MYT1L mutations destabilize neuronal cell fate and function, and are sufficient to cause ASD-associated phenotypes in human and mouse models,” the study authors concluded. “Hence, failure to silence non-neuronal gene expression in neurons represents a novel mechanism that, at least in part, could contribute to ASD etiology.”

The results of the study only apply to mice and lab-made human nerve cells, thus it is unclear if lamotrigine will work the same way in humans to treat autism.