Israeli Hospital Delivers World’s First Experimental Gene Therapy for Rare Genetic Epilepsy

The procedure at Schneider Children’s Medical Center of Israel in Petah Tikva marks a key advance in precision genetic therapies targeting rare neurological conditions.

By JUDY SIEGEL-ITZKOVICH

JUNE 9 2026

An eight-month-old infant with a rare genetic epilepsy has become the first patient worldwide to receive an experimental gene replacement therapy that restores WWOX gene function directly in the brain.

The procedure took place at Schneider Children’s Medical Center of Israel in Petah Tikva and represents an important step in creating targeted genetic treatments for uncommon neurological disorders.

The family declined to release any photos or personal details including the baby’s gender.

Only 60 to 90 genetically confirmed cases have been documented worldwide so far classifying the condition as an ultra-orphan disease.

The treatment stems from years of research led by Hebrew University of Jerusalem scientist Prof Rami Aqeilan.

Combining Discovery Clinical Skill and Global Teamwork

This achievement reflects the result of extensive basic and translational research. What started as an effort to understand a gene’s biological role has grown into a possible therapy for children facing one of the harshest forms of genetic epilepsy he said.

The success shows the strength of merging scientific discovery clinical skill and international teamwork he added. It illustrates how basic research can move from the lab toward new options for patients with rare genetic diseases.

WWOX-related epileptic encephalopathy known as WOREE syndrome occurs only when a child inherits two mutated copies of the gene one from each parent. Carriers with a single mutation usually show no symptoms yet can pass the variant to offspring. The disorder features drug-resistant seizures profound intellectual disability and major delays in motor skills.

Respiratory issues such as aspiration pneumonia remain the main cause of early death with severe cases typically surviving only two to four years.

Beyond its role as a tumor suppressor WWOX supports neuronal development and helps maintain the brain’s stable internal environment including temperature ion balance and energy regulation.

Additional symptoms often include severe muscle rigidity poor coordination and progressive microcephaly where head size falls below normal because brain growth halts.

Prof Aqeilan assembled a team of researchers clinicians and biotech experts from Israel and the United States including Dr Naama Orenstein and Dr Dror Kraus from Schneider plus Dr Yael Weiss CEO of Mahzi Therapeutics in San Francisco.

Mahzi Therapeutics focuses on rare genetic neurodevelopmental disorders. The company name drawn from the Greek word for together brings together patient groups academic teams industry partners and its own specialists to create therapies for these serious conditions.

WOREE Syndrome Early Drug-Resistant Epilepsy With High Mortality Risk

The infant appeared healthy at birth yet developed severe epileptic seizures at six weeks of age. Genetic tests confirmed a rare inherited defect in the WWOX gene causing WOREE syndrome marked by early-onset drug-resistant epilepsy major developmental impairment and elevated risk of early death.

Although the mutation in this case appears more common among people of Yemeni Jewish descent many other harmful WWOX variants exist globally and produce similar severe neurodevelopmental problems.

Originally studied for cancer biology the gene was later shown by Aqeilan’s team to be essential for normal brain development and neurological function.

Using mouse models lacking WWOX in the brain the lab demonstrated that gene loss leads to epilepsy developmental delay faulty myelination and early death closely matching symptoms seen in affected children.

Building on these results the team created a gene replacement approach using an AAV9 viral vector to deliver a healthy WWOX copy to neurons.

Preclinical tests showed that one dose restored gene expression reduced seizures improved neurological function and extended survival in animal models offering proof of concept for treating WWOX-related disease.

After academic development the technology was licensed to Mahzi Therapeutics which produced the clinical-grade vector and handled regulatory steps.

Following a compassionate-use request by Dr Orenstein and her team and after regulatory clearance the therapy was delivered directly into the infant’s brain.

One month later the child remained stable and left the hospital. No return of the severe seizures had occurred during this early period. Extended monitoring will assess long-term safety and benefit.

The advance rests on internationally recognized work from Aqeilan’s lab that identified WWOX as a key regulator of nervous system development. The research has received support including a European Research Council grant to move the therapy toward clinical use.

While the infant continues under close observation the treatment signals progress toward personalized options for rare genetic epilepsies and brings hope to families worldwide affected by WWOX disorders.