South Korean Scientists Discover Breakthrough Gene Therapy Targeting Brain Transporter to Treat Autism Spectrum Disorder
In a breakthrough discovery that challenges long-held assumptions about neurodevelopmental treatment timelines, scientists at South Korea's Institute for Basic Science (IBS) have developed a highly targeted gene therapy capable of reversing core symptoms of Autism Spectrum Disorder (ASD) in adult brains. Published in the prestigious journal Nature Communications, the research presents an innovative therapeutic approach that bypasses the severe side effects associated with previous medical trials.
Led by IBS Director Eunjoon Kim, the research team focused on restoring the function of N-methyl-D-aspartate receptors (NMDARs)—crucial brain components responsible for cellular communication, learning, and memory retention. Diminished NMDAR activity is heavily linked to autism as well as various other neurological conditions. While previous global efforts attempted to boost NMDAR function by blocking a transporter called GLYT1, those attempts resulted in adverse side effects, as GLYT1 is densely present in brain regions governing respiration and motor control.
To overcome this hurdle, the IBS team targeted 'SLC6A20', a glycine transporter predominantly localized in the cortex and hippocampus—the brain's primary hubs for cognitive processing. Utilizing Antisense Oligonucleotides (ASO) to inhibit SLC6A20, researchers successfully normalized NMDAR activity. The treatment was tested on mice with mutations in the SHANK2 and SHANK3 genes, which are associated with autism and neurological disorders such as Phelan-McDermid syndrome.
The results demonstrated marked improvements in social interaction and communication skills alongside a notable decrease in repetitive behaviors. Significantly, these therapeutic benefits were achieved in fully adult mice, proving that neurological deficits can still be successfully addressed long after brain development has completed.
To evaluate potential human application, the researchers replicated the trial on human cortical organoids—lab-grown brain models created using CRISPR gene-editing to carry SHANK2 and SHANK3 mutations. Upon receiving the ASO therapy targeting human SLC6A20, the organoids exhibited near-normal NMDAR functionality. Director Kim noted that targeting SLC6A20 controls internal brain signals directly, making it vastly more practical for real-world clinical application than complex gene-reexpression therapies.
The study further confirmed that a single dose of the ASO therapy maintained its effectiveness for at least eight weeks in test subjects without causing any observable adverse side effects. Phospho-proteomic analysis revealed that the treatment improved the functional mechanism of existing proteins rather than altering overall protein quantities. Beyond autism, reduced NMDAR activity plays a role in schizophrenia and various intellectual disabilities, opening avenues for broader psychiatric applications.