NCH’s AAV Gene Therapy Shows Early Promise in Neurodevelopment Disorders

December 04, 2025-AAV (adeno-associated virus) gene therapy has achieved a significant milestone, bringing rare optimism to the challenging field of neurodevelopmental disorders. Nationwide Children’s Hospital (NCH) in Columbus, Ohio, announced that 8-year-old Maxwell Freed became the first person to receive a gene therapy for SLC6A1, a rare condition causing seizures, developmental delays, and autism-like symptoms.

Preliminary results, just three months post-treatment, are highly encouraging: the medicine has reportedly improved Maxwell’s mood, muscle tone, and coordination, enabling him to achieve new developmental milestones, including riding a bike.

AAV Therapy Targets GABA Imbalance with “Goldilocks Approach”

The SLC6A1 gene helps regulate GABA, a key neurotransmitter in the brain that keeps nerve activity in balance. When the gene is dysfunctional, it can lead to epilepsy and autism-related symptoms. The gene therapy aims to correct this imbalance, offering a potential new path for treating related brain disorders.

The AAV therapy, developed by Allison Bradbury and Kathryn Meyer at Nationwide Children’s, utilizes a common AAV9 vector. Researchers employed a strategic delivery method to mitigate the inherent risks of central nervous system (CNS) gene therapy:

• Targeted Delivery: The AAV therapy was delivered through spinal fluid (intrathecally) rather than intravenous infusion.

• Low-Dose Strategy: This allowed for a lower dose of the AAV vector. As principal investigator Allison Bradbury explained, this requires a “Goldilocks approach,” ensuring enough of the AAV therapy is delivered to be therapeutic without overstimulating the CNS.

The progress contrasts with a setback in 2022 when Taysha Gene Therapies paused its separate SLC6A1 gene therapy in the preclinical stage, leaving families concerned about treatment access. Maxwell’s therapy was developed through a parallel, confidential collaboration between Nationwide Children’s and the patient’s mother’s nonprofit, SLC6A1 Connect.

Expanding Access and Managing Risk

The successful dosing of Maxwell, which was delivered as an “n-of-1” case (a clinical trial just for him), has energized efforts to expand the AAV therapy to a larger patient cohort. The Nationwide team manufactured enough AAV vector for an early-stage study with up to 10 patients. The foundation is currently focused on fundraising to continue development.

The complexity and inherent risk of CNS gene therapies were underscored by news that emerged the same day Maxwell was dosed: a patient died in an unrelated clinical trial testing a gene therapy for STXBP1 epileptic encephalopathy. This highlights the ongoing challenge of safe delivery, even with new capsid technologies designed to improve CNS targeting.

Experts note that if the preliminary results hold up, this pioneering AAV treatment could show a way forward in developing treatments for other neurodevelopmental disorders caused by faulty neurotransmitter regulation.