An eight-month-old infant with rare but severe epilepsy was cured after receiving an experimental gene replacement in a historic medical moment.
The child was one of the first in the world to be treated with gene replacement therapy to restore the function of a crucial gene that regulates nervous system development.
It was delivered via a delicate neurosurgical procedure that injected a functioning copy of the missing gene directly into the infant’s brain.
Although appearing healthy at birth, at 6 weeks old the boy started having severe epileptic seizures and showed severe developmental decline.
Testing revealed an inherited defect in the WWOX gene, which caused the neurological disorder WOREE syndrome (WWOX-related epileptic encephalopathy) that results in drug-resistant epilepsy and a high risk of premature death.
It took an international effort to treat the infant boy’s condition, bringing together scientists, clinicians and biotechnology leaders at Clalit-Schneider Children’s Medical Center in Israel.
The procedure required not only special approvals from health authorities and governing bodies across several countries, but also special dosing calculations tailored to the infant.
Professor Rami I. Aqeilan, an Arab researcher from the Hebrew University of Jerusalem, had been researching the gene’s role in cancer. He then discovered it also plays a critical role in neurological function and normal brain development.
This prompted him to develop a therapy that could restore the gene.
Preclinical studies found that a single administration of gene replacement restored WWOX expression and improved seizures, growth abnormalities, neurological deficits and survival in animal models.
After years of development and further research, the therapy was then licensed to a US biotech company, Mahzi Therapeutics.
“Families often ask us: If a child is missing a working gene, why can’t we simply give them one?” Dr. Naama Ornstein, head of the genetics unit at Clalit- Schneider, said in a press release.
“Usually, we have no answer. This time, for the first time in the world, we could.”
While common among those of Yemeni Jewish ancestry, WOREE is extremely rare, with only 60 to 90 genetic cases having been identified worldwide.
The child remained critically stable one month after treatment and was discharged from the hospital with no recurring seizures reported.
As the infant continues to be monitored, this represents a significant step in treating rare genetic epilepsies.
“[This achievement] highlights how fundamental research can advance from the laboratory toward potential new treatment options for patients with rare genetic diseases,” Aqeilan told News Medical.
