Endpoints News | Feb.23 2026 —Jaguar Gene Therapy has begun dosing young children in what appears to be the first clinical gene therapy study targeting a genetic form of autism spectrum disorder linked to SHANK3 deficiency (Phelan-McDermid syndrome), according to a recent Endpoints News report. The Chicago-based biotech has treated five children ages 2–4 and expects preliminary readouts later this year based on at least six months of follow-up in the initial cohort.
The program, JAG201, is designed to deliver a functional version of SHANK3, a gene critical for building and maintaining synaptic connections in the brain. In people with Phelan-McDermid syndrome, SHANK3 is deleted or dysfunctional, contributing to severe neurodevelopmental symptoms that can include intellectual disability, hypotonia, seizures, and major communication challenges. Endpoints reports Jaguar argued successfully to prioritize pediatric dosing rather than starting in adults, on the rationale that earlier treatment may be more beneficial during active brain development.
Jaguar’s approach uses an AAV9 vector (the same serotype used in Zolgensma) to deliver a modified SHANK3 construct into the brain. Because the full SHANK3 gene is too large for standard AAV packaging, the therapy uses an abridged “minigene” version developed from academic research. The treatment is administered via neurosurgical infusion into the lateral ventricle, with the goal of broad CNS distribution. Endpoints also notes key constraints familiar to CNS AAV programs, including one-time dosing due to anti-AAV immune responses and the need to time treatment carefully in early childhood brain development.
The trial could become a notable inflection point for autism drug development, a field that has historically seen many setbacks—particularly for broad-spectrum pharmacologic approaches. Jaguar’s strategy is more genetically targeted, focusing on a small but severe subgroup (Phelan-McDermid syndrome represents <1% of autism cases, per the Endpoints report). If early results show improvements in cognitive, motor, or social function, the company is expected to seek funding for a larger study.
Jaguar previously announced FDA IND clearance for JAG201 and later said it had received FDA agreement to proceed with pediatric patients (2+) with expansion into adults following the pediatric cohort.
