Decreased NMDA receptor activity is considered one of the key mechanisms associated with neurological and psychiatric diseases, including autism spectrum disorder, schizophrenia, intellectual disability, and other conditions. Numerous attempts to increase the activity of these receptors have thus far yielded limited results.
NMDA receptors require two signals to function properly: glutamate and glycine. Previously, scientists tried to increase glycine levels by blocking the GlyT1 transporter, but this was ineffective. They are now focusing on another transporter called Slc6a20a. Unlike GlyT1, it functions in the cerebral cortex and hippocampus, which play an important role in cognitive function.
The treatment was tested on mouse models with mutations in the SHANK2 and SHANK3 genes, which are considered among the most significant risk factors for the development of autism.
The therapy successfully restored NMDA receptor activity.
Scientists also recorded improvements in behavior: the animals showed increased social interaction and communication, and a decrease in the severity of repetitive behavior.
Importantly, the therapy maintained its effectiveness in adult animals, indicating the potential of the treatment even after the completion of key stages of brain development. Another important finding was the reproducibility of the effect in human brain organoids, which also demonstrated reduced NMDA receptor activity.
Because decreased NMDA receptor activity is observed in other disorders, including schizophrenia and intellectual disability, the therapy has the potential to be used more broadly beyond the treatment of ASD.
Previously, other scientists have shown that brain changes in people with autism are unique and highly complex.
