In a hospital in Israel, an eight-month-old child became the first human being to receive a gene therapy aimed at correcting the broken WWOX gene responsible for WOREE syndrome — a rare and often fatal form of epilepsy that had seized his life since he was six weeks old. The treatment, delivered directly into the brain after more than a decade of laboratory research, represents the long arc from scientific curiosity to clinical hope. One month on, the child was discharged stable and seizure-free, a fragile but meaningful threshold in the longer story of whether genetic medicine can reach the m
First-ever gene therapy for rare epilepsy successfully delivered to infant's brain
The 8-month-old patient suffered severe drug-resistant epileptic seizures beginning at 6 weeks of age that threatened development and survival before receiving treatment.
What began as curiosity became a lifeline for the most severe genetic epilepsy
Mark
Why does this particular gene matter so much? What does WWOX actually do in the brain?
Mimi
It's essential for normal brain development and function—we're still learning exactly how. What we know is that when it's missing or broken, neurons don't develop properly, the insulation around nerve fibers fails, and seizures emerge. The gene was originally studied in cancer research, but Aqeilan's work showed it's equally critical for the nervous system.
Mark
How did they decide this infant was the right first patient?
Mimi
The child had a clear genetic diagnosis, severe drug-resistant seizures, and a mutation that the research team had specifically studied in animal models. There was a biological rationale for why this therapy might work in this case. And the family was willing to accept the risks of an experimental treatment when the alternative was watching their child's condition worsen.
Mark
What happens now? Is one month of stability enough to call this a success?
Mimi
It's a promising beginning, but not a success yet. They need years of follow-up to see if the therapy's effects last, if the child's development normalizes, if complications emerge later. The real question is whether this first case opens a pathway for other children with WOREE syndrome or similar genetic epilepsies.
Mark
Why is this particular mutation more common in Yemeni Jewish populations?
Mimi
That's a matter of genetics and ancestry—certain mutations accumulate in populations that have been geographically or socially isolated. But the research team emphasizes that WWOX mutations exist worldwide, so the implications of this therapy extend far beyond one ethnic group.
Mark
What was the biggest technical hurdle—getting the virus into the brain, or something else?
Mimi
Delivering genetic material to the right neurons in an infant's developing brain is extraordinarily delicate. But the real challenge was the years of research proving the concept would work at all. Once they had that, the clinical execution became possible.
O Pulso
- A child born apparently healthy began suffering severe, drug-resistant seizures at just six weeks old — a neurological emergency that standard medicine could not stop.
- The diagnosis of WOREE syndrome, caused by a rare WWOX gene mutation, historically offered families little more than a prognosis of deterioration and early death.
- Over a decade of research — from mouse models at Hebrew University to a licensed biotechnology company — compressed into a single, extraordinarily delicate injection into an infant's developing brain.
- One month after the procedure, the child left the hospital without the catastrophic seizures that had defined his short life, offering the family a moment of genuine, if cautious, relief.
- The medical and scientific community now watches closely, knowing that long-term monitoring will determine whether this first case becomes a template for personalized genetic therapies in rare neurological disease worldwide.
In a hospital in Israel, an eight-month-old child became the first human being to receive a gene therapy aimed at correcting the broken WWOX gene responsible for WOREE syndrome — a rare and often fatal form of epilepsy that had seized his life since he was six weeks old. The treatment, delivered directly into the brain after more than a decade of laboratory research, represents the long arc from scientific curiosity to clinical hope. One month on, the child was discharged stable and seizure-free, a fragile but meaningful threshold in the longer story of whether genetic medicine can reach the most vulnerable patients before the disease does.
An eight-month-old boy in Israel has become the first person in the world to receive a gene therapy designed to treat WOREE syndrome, a rare and devastating genetic epilepsy. The child appeared healthy at birth, but at six weeks old, severe seizures began — ones that resisted every standard medication. Genetic testing identified the cause: inherited mutations in the WWOX gene, a defect found across populations but particularly prevalent among people of Yemeni Jewish descent. For families who receive this diagnosis, it has historically meant watching a child's neurological function erode with almost nothing to offer in return.
The road to this moment began more than a decade ago at the Hebrew University of Jerusalem, where Prof. Rami Aqeilan was studying the WWOX gene in cancer biology. His research pivoted when he discovered the gene's critical role in brain development. Using mice engineered without the gene, his team reproduced the full picture of WOREE syndrome — seizures, developmental delay, defective nerve insulation, early death — and showed that restoring the gene's function could reverse those outcomes. The technology was eventually licensed to Mahzi Therapeutics, which produced a clinical-grade therapy using an AAV9 viral vector to carry a healthy WWOX gene directly into brain neurons.
The decision to treat this particular infant came through a compassionate-use program at Schneider Children's Medical Center, led by Dr. Naama Orenstein and her colleagues. After extensive regulatory preparation, the therapy was injected directly into the child's brain — a technically demanding procedure in an infant's still-developing nervous system. One month later, the child had not experienced a recurrence of the severe seizures that had threatened his survival. He was discharged from the hospital, clinically stable.
This is not yet a cure. Long-term monitoring will be essential to determine whether the effects persist, whether complications emerge, and whether the child's development proceeds normally. But for a family facing one of the most severe diagnoses in pediatric neurology, it is a beginning — and for a field watching closely, it may be the first step toward personalized genetic therapies for rare neurological disorders around the world.
An 8-month-old child in Israel has become the first person on earth to receive a gene therapy designed to treat a rare and devastating form of epilepsy by repairing a broken gene directly inside the brain. The infant, who carries mutations in the WWOX gene that cause WOREE syndrome, received the experimental treatment at Schneider Children's Medical Center after years of research and regulatory preparation. One month after the procedure, the child remained stable in the hospital and was discharged without experiencing the severe seizures that had dominated his first months of life.
The child appeared normal at birth. At six weeks old, seizures began—severe ones that did not respond to standard epilepsy medications. Genetic testing revealed the culprit: a rare inherited defect in the WWOX gene, a mutation particularly common among people of Yemeni Jewish descent but found in populations worldwide. WOREE syndrome, as the condition is called, is characterized by early-onset seizures that resist treatment, profound delays in development, and a high risk of early death. For families carrying this mutation, the diagnosis has historically meant watching a child's neurological function deteriorate with few options to intervene.
The path to this first treatment began more than a decade ago in a laboratory at the Hebrew University of Jerusalem, where Prof. Rami Aqeilan was studying the WWOX gene in the context of cancer biology. His research took an unexpected turn when he discovered that WWOX plays a critical role in brain development and function—not just in tumor suppression. Using mice engineered to lack the gene in their brains, Aqeilan's team demonstrated that loss of WWOX caused the same constellation of problems seen in children with WOREE syndrome: seizures, developmental delay, defective nerve insulation, and premature death. The findings suggested that restoring the gene's function might reverse or prevent these catastrophic outcomes.
The research team designed a delivery system using a modified virus—an adeno-associated viral vector, or AAV9—to carry a healthy copy of the WWOX gene into brain neurons. In animal studies, a single injection restored the gene's expression and improved seizures, neurological function, growth, and survival. The proof of concept was solid enough to license the technology to Mahzi Therapeutics, a biotechnology company that manufactured the clinical-grade therapy and navigated the regulatory pathway toward human use.
The decision to treat this particular infant came through a compassionate-use program initiated by Dr. Naama Orenstein and colleagues at Schneider Children's Medical Center. After extensive preparation and regulatory approvals, the therapy was injected directly into the child's brain. The procedure itself was a technical achievement—delivering genetic material to the right neurons in an infant's developing brain is extraordinarily delicate work. But the real test would come in the weeks and months that followed.
One month after treatment, the child had not experienced a recurrence of the severe seizures that had previously threatened his development and survival. He remained clinically stable and was discharged from the hospital. This is not yet a cure—long-term monitoring will be essential to understand whether the therapy's effects persist, whether complications emerge, and whether the child's development proceeds normally. But it is a beginning. For a family facing a diagnosis that historically meant watching their child deteriorate, it is a moment of genuine hope.
The achievement represents the convergence of multiple forces: fundamental research into how genes shape the nervous system, clinical expertise in treating rare pediatric neurological disease, regulatory systems willing to move carefully but not glacially, and international collaboration among scientists and companies. Prof. Aqeilan described the moment as the culmination of work that began as pure curiosity about a gene's function and evolved into a potential lifeline for children with one of the most severe forms of genetic epilepsy. The research has received international support, including a European Research Council grant aimed at advancing the therapy further. As the infant continues to be monitored, the field watches to see whether this first case opens a pathway toward personalized genetic therapies for rare neurological disorders worldwide.
Citações Notáveis
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.— Prof. Rami Aqeilan
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