June 08, 2026 —
An eight-month-old infant with severe genetic epilepsy has become the first patient in the world to receive an experimental AAV9 gene replacement therapy designed to restore WWOX gene function directly in the brain. The treatment was administered at Schneider Children’s Medical Center of Israel under a compassionate-use program.
The child was diagnosed with WOREE syndrome, or WWOX-related epileptic encephalopathy, a rare and devastating neurodevelopmental disorder caused by inherited defects in the WWOX gene. The infant appeared healthy at birth but began experiencing severe epileptic seizures at six weeks of age. Genetic testing later confirmed a disease-causing WWOX mutation.
WOREE syndrome is characterized by early-onset, drug-resistant epilepsy, profound developmental impairment, and a high risk of premature death. Although the specific mutation in this case is more prevalent among individuals of Yemeni Jewish ancestry, multiple pathogenic WWOX variants have been identified worldwide and are associated with severe neurodevelopmental disease.
The therapy is based on more than a decade of research led by Prof. Rami Aqeilan at the Hebrew University of Jerusalem. While WWOX was originally studied for its role in cancer biology, Aqeilan’s laboratory helped establish that the gene is also essential for normal brain development and neurological function. In mouse models lacking WWOX expression in the brain, researchers observed epilepsy, developmental delay, defective myelination, and premature death, closely mirroring symptoms seen in children with WOREE syndrome.
Building on these findings, the research team developed a gene replacement strategy using an AAV9 vector to deliver a healthy copy of the WWOX gene to neurons. In preclinical studies, a single administration restored WWOX expression and improved seizures, neurological deficits, growth abnormalities, and survival in animal models.
The technology was later licensed to Mahzi Therapeutics for manufacturing and translational development. After extensive preparation and regulatory approvals, the gene therapy was administered directly into the infant’s brain.
One month after treatment, the child remained clinically stable and was discharged from the hospital. No recurrence of the severe seizures that had previously threatened his development and survival had been reported during the initial observation period. Long-term follow-up will be required to evaluate safety, durability, and therapeutic benefit.
The case represents an important milestone for precision AAV gene therapy in ultra-rare neurological disorders. While it remains an early compassionate-use treatment in a single patient, the program highlights how academic discovery, patient-centered clinical care, biotechnology development, and international collaboration can converge to create potential therapeutic options for devastating genetic diseases.
