An eight-month-old Israeli infant has become the first patient in the world to receive an experimental gene therapy that researchers say could pave the way for treating severe and previously untreatable forms of genetic epilepsy.
The therapy was administered at Schneider Children’s Medical Center in Petah Tikvah under a compassionate-use framework, allowing treatment outside a formal clinical trial because of the severity of the child’s condition and following extensive regulatory approvals.
The treatment delivers a healthy copy of the WWOX gene directly into brain neurons through a single injection, with the goal of restoring a function essential for normal neurological development. Mutations in the gene can cause severe early-onset epilepsy and profound developmental impairment, including WOREE syndrome (WWOX-related epileptic encephalopathy), a rare neurodevelopmental disorder.
The infant appeared healthy at birth but began experiencing severe epileptic seizures at six weeks of age. Genetic testing later identified a rare inherited mutation in the WWOX gene, confirming a diagnosis of WOREE syndrome.
The disorder is characterized by epilepsy that is typically resistant to medication, severe developmental impairment and a high risk of premature death.
From lab to patient
Professor Rami Aqeilan of the Hebrew University of Jerusalem, who led the research, told TPS-IL that an application to the U.S. Food and Drug Administration for a treatment based on the approach is expected to be submitted within two months.
“We are very proud. We listed this patent after we proved its concept on mice. The treatment for the infant was made possible as a compassionate-use treatment, thanks to my colleague Dr. Naama Orenstein,” Aqeilan said.
“The infant is the first human to receive this treatment. The FDA process will include phases of clinical trials and we expect that within two or three years, if everything goes according to plan, there will be a medicine.”
The work is based on more than a decade of research led by Aqeilan at the Lautenberg Center for Immunology and Cancer Research at the Hebrew University’s Faculty of Medicine, bringing together scientists, clinicians and biotechnology partners in Israel and the United States.
Originally studied for its role in cancer biology, WWOX was later identified by Aqeilan’s team as essential for normal brain development and neurological function, helping establish the scientific basis for exploring gene-replacement strategies in severe neurodevelopmental disorders.
Mouse models lacking WWOX expression in the brain developed severe neurological abnormalities, including developmental delays, epilepsy, defective myelination and premature death. Researchers said these findings closely mirrored symptoms observed in children with WOREE syndrome.
The results helped establish the scientific basis for a gene-replacement strategy aimed at restoring WWOX function in the brain.
In preclinical studies, a single administration of the therapy restored WWOX expression and improved seizures, neurological deficits, growth abnormalities and survival in animal models, Aqeilan said.
According to the Hebrew University, the child remained clinically stable one month after treatment and was discharged from the hospital. No recurrence of the severe seizures previously observed in the infant was reported during that period.
Researchers cautioned that long-term follow-up will be needed to evaluate both the safety and effectiveness of the therapy.
“This gives hope to many patients who not only have this syndrome, but also other neurodevelopmental problems. Gene therapy can be the answer to many of these diseases. We must continue working to promote it,” Aqeilan told TPS-IL.
