New autism therapy shows surprising benefits even in adult mice

A recent study led by IBS Center for Synaptic Brain Dysfunctions Director Eunjoon Kim has uncovered a potential new treatment for autism spectrum disorder (ASD) by targeting a specific brain receptor. The researchers focused on a glycine transporter called Slc6a20a/SLC6A20, which plays a crucial role in restoring NMDA receptor (NMDAR) function.

NMDARs are vital for learning, memory, and cognitive processes, and their dysfunction is linked to various neurological and psychiatric conditions, including ASD, schizophrenia, intellectual disability, and NMDAR encephalitis. Previous treatments have been inconsistent and often caused side effects due to their broad targeting. This study utilized antisense oligonucleotides (ASOs) to reduce Slc6a20a expression, which was found to be more effective in brain regions involved in cognition, such as the cortex and hippocampus.

The treatment improved NMDAR activity and alleviated social interaction, communication, and repetitive behavior issues in adult mice models with autism-related mutations in SHANK2 and SHANK3 genes. The researchers observed that the therapy caused minimal changes in total protein amounts but rather corrected abnormal phosphorylation patterns in proteins regulating synaptic signaling and NMDARs.

Similar results were seen in human cortical organoids with SHANK2 or SHANK3 mutations. The findings suggest that this approach may offer a more practical therapeutic route for neurodevelopmental disorders characterized by NMDAR hypofunction, potentially extending its applications to other disorders like schizophrenia and certain forms of intellectual disability.