PETAH TIKVA — An eight-month-old infant received an experimental gene replacement therapy designed to restore WWOX gene function in the brain at Schneider Children's Medical Center in Petah Tikva. The infant was discharged from the hospital one month after receiving the therapy, at which point the child was clinically stable.
The gene replacement therapy, which uses an adeno-associated viral vector (AAV9), delivers a functional WWOX gene copy to neurons. Genetic testing identified an inherited defect in the WWOX gene causing WOREE syndrome in the infant, who began experiencing epileptic seizures at six weeks of age. No recurrence of severe seizures was reported during the initial one-month observation period.
Dr. Naama Orenstein of Schneider Children's Medical Center initiated a compassionate-use program for the patient following regulatory approvals. Dr. Orenstein and Dr. Dror Kraus participated in the clinical administration of the treatment. The therapy technology was licensed by Mahzi Therapeutics, which also manufactured the clinical-grade gene therapy vector. Dr. Yael Weiss serves as the chief executive officer of Mahzi Therapeutics.
Prof. Rami Aqeilan led the underlying research at the Hebrew University of Jerusalem. Preclinical studies in mouse models demonstrated that a single administration improved seizures, neurological deficits, growth abnormalities, and survival. Professor Aqeilan said: "This moment represents the culmination of many years of basic and translational research. What began as an effort to understand the biological function of a gene has evolved into a potential therapeutic strategy for children affected by one of the most severe forms of genetic epilepsy." The research received funding from a European Research Council Proof-of-Concept grant.
WOREE syndrome requires inheriting two mutated copies of the WWOX gene. Symptoms of the syndrome include drug-resistant epilepsy, profound intellectual disability, and severe psychomotor delays. Respiratory complications are the leading cause of premature death in patients with WOREE syndrome. The average lifespan for severe WOREE syndrome cases is generally two to four years. The specific mutation treated in this case is prevalent among individuals of Yemeni Jewish ancestry. Medical literature contains an estimated 60 to 90 genetically confirmed cases of WOREE syndrome worldwide.