The treatment was given at Schneider Children's Center to an eight-month-old baby with WOREE syndrome, a rare disease caused by a defect in the WWOX gene. The development is based on more than a decade of research led by Prof. Rami Aqilan of the Hebrew University
An eight-month-old baby with a rare and severe genetic epilepsy has received an experimental gene therapy in Israel designed to insert a healthy copy of the WWOX gene directly into the brain. The treatment was administered as part of a compassionate use program at Schneider Children's Medical Center, and is being billed as the first of its kind in the world to restore the activity of this gene in the brain of a patient with WOREE syndrome. According to the Hebrew University, the technology is based on years of research in the laboratory of Prof. Rami Aqilan of the Faculty of Medicine, and was later developed for clinical application by Mahzi Therapeutics. (openscholar.huji.ac.il)
The baby appeared healthy at birth, but at six weeks of age he began to suffer from severe epileptic seizures. Genetic testing revealed a rare inherited defect in the WWOX gene, which caused WOREE syndrome, short for WWOX-related epileptic encephalopathy. This is a severe neurological syndrome that appears very early in life and is characterized by drug-resistant epilepsy, profound developmental impairment and a high risk of early death.
From cancer to the brain
The WWOX gene was initially studied primarily in the context of cancer biology. Prof. Aqilan's work has expanded our understanding of it and shown that it is also essential for normal brain development and nervous system function. In mouse models in which the gene was silenced in the brain, symptoms similar to those seen in children with WOREE syndrome appeared: severe seizures, developmental delay, myelin damage, and early death.
Based on these findings, the researchers developed a gene replacement strategy: using a transgenic AAV9 virus as a carrier, whose function is to deliver a normal copy of WWOX to nerve cells. In preclinical studies in mice, a single administration of the treatment restored WWOX expression and improved seizures, neurological functions, growth, and survival. A study published in EMBO Molecular Medicine described rescue of symptoms in a mouse model of WWOX deficiency after gene delivery using AAV9. (PMC)
Prof. Rami Aqilan said, “This moment represents the culmination of many years of basic and translational research. What began as an attempt to understand the biological role of a gene has evolved into a possible therapeutic strategy for children with one of the most severe forms of genetic epilepsy.”
Compassionate care, not full clinical proof
After years of research and development, the technology was licensed to Mahzi Therapeutics, which manufactured the clinical-grade gene vector and supported the medical translation and regulatory processes. The clinical process was led by Dr. Naama Orenstein and her colleagues at Schneider Children’s Medical Center, in collaboration with Dr. Dror Kraus, Dr. Yael Weiss, CEO of Mahzi Therapeutics, and other teams from Israel and the United States.
The treatment was administered directly to the baby's brain after extensive preparations and regulatory approvals. One month after the treatment, the child was reported to be clinically stable and discharged from the hospital. During the initial observation period, there was no recurrence of the severe seizures that had threatened his development and life. However, this was a very short follow-up, and therefore long-term follow-up is needed to assess the safety of the treatment and its effectiveness in practice.
This distinction is important: This is a significant medical and scientific step, but it is not yet a proven treatment available to the general public. Gene therapies for rare diseases sometimes progress from basic research to individualized compassionate use, but the path to demonstrating safety and broad efficacy requires long-term follow-up, data collection, and sometimes additional clinical trials.
A door to personalized medicine in rare diseases
WWOX therapy joins a broader trend in genetic medicine: the attempt to develop precision treatments for rare diseases caused by a defect in a single gene. In such diseases, identifying the defective gene may allow the development of a treatment that directly targets the disease mechanism, rather than just relieving symptoms.
In the case of WOREE, the disruption of the WWOX gene prevents the proper functioning of a protein needed by the nervous system. Therefore, the therapeutic idea is to provide the nerve cells with a healthy copy of the gene, in the hope that they will be able to regenerate the missing protein. Mahzi Therapeutics notes that it is developing, in collaboration with Aqilan’s lab at the Hebrew University, an AAV9-based approach to gene replacement in WWOX-related diseases. (Mahzi Therapeutics)
Prof. Aqilan said that the achievement “demonstrates the power of combining scientific discovery, clinical excellence, and international collaboration,” and that it illustrates how basic research can advance from the laboratory toward new treatment options for rare genetic diseases.
The child will continue to be closely monitored by doctors. Even if the initial results are encouraging, the broader significance of the treatment will only become clear later: whether it is safe over time, whether it changes the course of the disease, and whether a similar approach can be adapted for other children with different WWOX mutations.
Short FAQ:
What is WOREE syndrome?
WOREE syndrome is a rare neurological disease caused by a mutation in the WWOX gene. It appears at an early age and is characterized by severe epilepsy, developmental delay, and a high risk of serious complications.
What is the purpose of gene therapy?
The treatment is designed to transfer a normal copy of the WWOX gene to nerve cells in the brain, to enable production of the missing or defective protein.
How is the gene transferred to the brain?
The approach is based on an AAV9 viral vector, which serves as a carrier for transferring a normal copy of the gene to cells.
Is this a proven treatment?
Not yet. This is an experimental treatment given under compassionate use to a single patient. Long-term follow-up is needed to assess safety and efficacy.
Who is behind the development?
The development is based on research led by Prof. Rami Aqilan from the Hebrew University, in collaboration with doctors from Schneider Children's Medical Center and Mahzi Therapeutics.
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