Blocking SLC6A20 Boosts NMDA Receptor Function and Improves Autism Behaviors in Mice

A study from the Institute for Basic Science demonstrates that targeting the glycine transporter SLC6A20 can correct NMDA receptor hypofunction linked to autism spectrum disorder. By applying antisense oligonucleotides to lower SLC6A20 expression, the researchers re-established normal receptor activity in mouse models with SHANK2 or SHANK3 mutations, leading to marked improvements in social, communicative and repetitive behaviors, effects that persisted for at least eight weeks.

Phospho-proteomic analysis suggested the therapy normalizes protein signaling rather than altering protein abundance. Human cortical organoids engineered with the same mutations responded similarly, with NMDA receptor activity returning to near-normal levels. No adverse effects were observed in treated mice during the study period. The findings propose SLC6A20 inhibition as a precise, potentially translatable approach for neurodevelopmental disorders characterized by NMDA receptor deficits.