Researchers discovered a new way to treat autism by fixing a tiny protein that moves a chemical called glycine inside brain cells. The protein is named Slc6a20a (also called SLC6A20).
Why This Protein Matters
The brain needs a special door called the NMDA receptor to let messages travel between cells. This door works best when two helpers, glutamate and glycine, are present. In autism, the NMDA door often does not open well, which can make learning and memory harder.
Earlier attempts tried to raise glycine levels by blocking another transporter, GlyT1. Unfortunately, GlyT1 is found in parts of the brain that control breathing and movement, so those treatments caused side effects.
Slc6a20a lives mainly in the cortex and hippocampus – areas that handle thinking and memory. Targeting this protein could improve the NMDA door without disturbing other important brain functions.
How the Scientists Tested the Idea
They used short DNA pieces called antisense oligonucleotides (ASOs) to lower the amount of Slc6a20a in mice. The mice had mutations in the autism‑risk genes SHANK2 or SHANK3, which also affect the NMDA receptor.
After the treatment, the mice showed stronger NMDA activity. Their social behavior got better, they communicated more, and they repeated fewer actions. Even adult mice improved, suggesting the brain can still be helped after it has mostly finished growing.
What Happens Inside the Brain
Large‑scale tests of protein changes showed that the therapy did not dramatically increase or decrease the amount of proteins. Instead, it corrected the way some proteins were switched on or off (phosphorylation). This fine‑tuning restored normal signaling without a massive overhaul.
Human Brain Mini‑Organs Show Promise
To see if the method might work in people, the team made tiny brain pieces (organoids) from human cells and gave them the same SHANK2 or SHANK3 mutations. These organoids also had weak NMDA activity.
When the researchers added an ASO that targets the human SLC6A20 gene, the NMDA door opened almost as well as in healthy organoids. This shows the approach could one day help humans with autism or similar disorders.
Long‑Lasting and Safe
A single dose of the ASO stayed effective for at least eight weeks in mice, and no harmful effects were seen during that time.
Because low NMDA activity is also linked to schizophrenia and some intellectual disabilities, this therapy might one day help many brain conditions.
Overall, lowering Slc6a20a appears to be a safe and powerful way to boost NMDA receptor function, offering hope for new treatments for autism and other neurodevelopmental disorders.