Quick summary: Israeli doctors have successfully delivered a functioning copy of a missing gene directly into the brain of an eight month old infant suffering from the otherwise fatal genetic disorder WOREE syndrome, marking a global first in personalised genetic medicine. The pioneering neurosurgical procedure utilized a specially engineered viral vector to deliver the therapy, resulting in clinical stability and a cessation of the severe, drug resistant epileptic seizures that previously threatened the patient’s survival. This medical milestone provides a transformative blueprint for global healthcare practice and public policy frameworks regarding ultra-orphan diseases, demonstrating that cross-cultural scientific collaboration and expedited regulatory approvals can successfully bring disease modifying gene therapies to vulnerable pediatric populations who previously faced certain premature death.
Doctors in Israel have become the first in the world to treat an eight-month-old baby with a fatal genetic brain disorder by injecting a healthy copy of the missing gene directly into his brain.
The pioneering procedure took place at Clalit Schneider Children’s Medical Center, part of Clalit Health Services, Israel’s largest health organisation, which runs 14 hospitals and 1,600 community clinics nationwide.
The infant, from an ultra-Orthodox Jewish family, had been diagnosed with WOREE syndrome, also known as WWOX-related epileptic encephalopathy, a devastating condition caused by biallelic mutations in the WWOX gene. It leads to early-onset, drug-resistant epilepsy, profound developmental impairment, and a high risk of premature death. Only 60–90 genetically confirmed cases have been identified worldwide, making it an ultra-orphan disease.
The baby appeared healthy at birth but began experiencing severe epileptic seizures at around six weeks old, alongside serious developmental decline. Genetic testing confirmed the rare inherited defect in the WWOX gene.
Dr Naama Ornstein, head of the genetics unit at Clalit Schneider, immediately recognised the disorder. Years earlier, she had treated another child with the same condition, but at that time no experimental therapy was available, and the child died. Dr Dror Kraus, senior physician in the neurology unit and an epilepsy specialist, has been closely monitoring and treating the infant since admission.
Determined to offer hope, Dr Ornstein contacted Professor Rami I. Aqeilan, an Arab researcher at the Hebrew University of Jerusalem, whose foundational academic work on the WWOX gene had revealed its critical importance in brain development and neuronal function. The gene is also known for its role as a tumour suppressor. This research evolved into a clinical therapy developed by Mahzi Therapeutics, an American biotech company led by Israeli-born CEO Dr Yael Weiss, which focused on manufacturing clinical-grade material and supporting translational efforts for underserved rare genetic neurodevelopmental disorders.
An extraordinary international effort involving physicians, researchers, regulators, and biotech leaders secured special emergency approval for the treatment, which had never before been administered to a human. Approvals were obtained from Israeli health authorities, the Ministry of Health, the Helsinki Committee, and international oversight bodies.
In a delicate neurosurgical procedure, Dr Ido Ben-Zvi from the neurosurgery unit at Clalit Schneider injected a functioning copy of the missing WWOX gene directly into the baby’s brain using a specially engineered adeno-associated viral vector, AAV9, designed to target the central nervous system. Dosage calculations were extraordinarily precise, tailored to the infant’s brain size.
“This was much more than a medical procedure,” said Dr Ornstein. “It was a fight for a child’s chance to smile, develop, and live. Families often ask us if a child is missing a working gene, why can’t we simply give them one. Usually we have no answer. This time, for the first time in the world, we could.”
The WWOX gene plays a vital role in neuronal development and maintaining the brain’s internal equilibrium. Preclinical studies in mouse models and patient-derived brain organoids by Professor Aqeilan’s team had shown that restoring WWOX expression could rescue severe neurological abnormalities, including epilepsy, developmental delay, and survival outcomes.
The baby has since been discharged home. One month after treatment, he remained clinically stable, with no reported recurrence of the severe seizures that had previously threatened his development. Long-term follow-up will be essential to assess ongoing safety and efficacy.
The case is described as a landmark moment in personalised genetic medicine, highlighting a rare convergence of science, humanity, and cross-cultural cooperation. The collaboration between an Israeli physician, an Arab scientist, and an Israeli-born biotech CEO exemplifies the kind of partnership needed to advance care for ultra-rare conditions. This breakthrough builds on more than a decade of research and represents a significant step forward in gene therapies for rare genetic epilepsies, where previously no disease-modifying treatments existed. Clalit Health Services continues to support monitoring and potential future cases as the field evolves.