An 8-month-old infant in Israel has become the first person in the world to receive a groundbreaking gene therapy that restores a missing gene directly to the brain—a milestone that could reshape treatment for one of the most severe forms of genetic epilepsy. The child, who developed devastating seizures at just 6 weeks of age, received the experimental treatment at Schneider Children's Medical Center of Israel after years of basic research finally found a path from laboratory to bedside.
The infant was born healthy but began experiencing drug-resistant seizures caused by a rare inherited defect in the WWOX gene, which triggers WOREE syndrome—a condition characterized by early-onset epilepsy, profound developmental delays, and a high risk of premature death. Genetic testing revealed the specific mutation, one that is particularly common among individuals of Yemeni Jewish ancestry, though similar disease-causing variants of the WWOX gene have been identified worldwide in families facing this devastating neurological disorder.
The therapy itself represents the payoff of more than a decade of research led by Prof. Rami Aqeilan of the Lautenberg Center for Immunology and Cancer Research at the Hebrew University of Jerusalem. His team, working alongside clinicians including Dr. Naama Orenstein and Dr. Dror Kraus at Schneider Children's Medical Center, discovered that WWOX is essential for normal brain development and neurological function—a role entirely separate from the gene's previously known involvement in cancer biology. Using genetically engineered mouse models that lacked WWOX expression in the brain, Aqeilan's laboratory reproduced the same neurological abnormalities seen in children with WOREE syndrome: severe epilepsy, developmental delay, defective nerve insulation, and premature death.
Building on these findings, the research team developed a precision delivery system using an adeno-associated viral vector—essentially a harmless virus redesigned as a molecular shuttle—to carry a healthy copy of the WWOX gene directly into neurons. In preclinical studies, a single administration restored the gene's function and improved seizures, neurological deficits, growth problems, and survival in animal models. The technology was eventually licensed to Mahzi Therapeutics, led by CEO Dr. Yael Weiss, which manufactured the clinical-grade therapy and navigated the regulatory pathway required to treat the infant through a compassionate-use program.
The results so far are cautiously promising. One month after the therapy was administered directly into the infant's brain, the child remained clinically stable and was discharged from the hospital. Critically, no recurrence of the severe seizures that had previously threatened his life and development was reported during this initial observation period. Long-term follow-up will be necessary to fully evaluate safety and lasting efficacy, but this moment marks a watershed in translational medicine—when fundamental biological discovery becomes a treatment that changes a child's trajectory.
For the global epilepsy community, particularly families dealing with rare genetic forms of the disease, this represents both an immediate breakthrough and a proof of concept. It demonstrates that even the rarest genetic disorders can be targets for precision medicine when research teams combine sustained scientific investigation with clinical expertise and international collaboration. As Prof. Aqeilan reflected on the achievement, the work reminds us that understanding the basic biology of a disease, pursued patiently over years, can eventually transform into hope for the families most affected.