A Pathway to Improving Core Symptoms of Autism Unveiled... IBS Presents New Therapeutic Strategy [Reading Science]

Recovery of Neural Function Confirmed in Mouse and Human Brain Organoids
Therapeutic Effects Seen Even in Adult Models, Suggesting Possibility for Autism Treatment Development

The research team at the Institute for Basic Science (IBS) has presented a new therapeutic strategy that could improve the core symptoms of autism spectrum disorder. By using a drug that regulates glycine levels in the brain, they improved behavioral symptoms in a mouse model of autism and also confirmed the recovery of neural function in human brain organoids.

The team led by Eunjoon Kim, Director of the Synaptic Brain Disease Research Center at IBS and Distinguished Professor at the Department of Biological Sciences at KAIST, focused on the 'NMDA receptor hypofunction' hypothesis, which is a leading theory for autism onset mechanisms. The NMDA receptor is a protein crucial for signal transmission between nerve cells as well as learning and memory. It is well known that reduced NMDA receptor function is associated with various brain disorders including autism, schizophrenia, and intellectual disabilities.

Treatment of Symptoms in Autism Spectrum Disorder Model by Slc6a20a-ASO. Social interaction problems, excessive/repetitive grooming, and reduced NMDA receptor activity were restored by Slc6a20a-ASO. Courtesy of the research team

To overcome the limitations of existing therapeutic strategies, the researchers targeted 'Slc6a20a', a glycine transporter predominantly distributed in brain regions associated with cognitive function. When the team administered a drug that inhibits this transporter to mouse models of autism and Phelan-McDermid syndrome, they found that NMDA receptor function was restored to normal levels after four weeks.

Deficits in social behavior and repetitive actions were also improved. Notably, even a single dose produced effects that lasted for more than eight weeks, and the function of synaptic proteins was also restored to normal levels.

Same Effect Observed in Human Brain Organoids

To confirm whether the same effect could be observed in humans, the team engineered human cerebral organoids with autism-related gene mutations and conducted experiments.

As a result, NMDA receptor function, which had been impaired in the organoids, was restored to normal levels after drug treatment. The researchers explained that this demonstrates the recovery of NMDA receptor function could serve as a core strategy for autism treatment.

Particularly noteworthy is that this study confirmed the therapeutic effect even in adult mouse models. While there had been skepticism about the possibility of treatment after adulthood, since autism is a neurodevelopmental disorder formed during development, this study showed that relevant brain functions and behavioral symptoms can still be improved even after development has concluded.

Eunjoon Kim, Director of the IBS Synaptic Brain Disease Research Center and Distinguished Professor at KAIST, said, "This study confirmed the improvement of behavioral symptoms in autism model mice and the restoration of neural function in human cerebral organoids through glycine-regulating drugs," adding, "We expect this to lay the foundation for the development of treatments targeting the core symptoms of autism spectrum disorder in the future."

The research results were published in the international journal Nature Communications.

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