An eight-month-old Israeli baby has become the first person in the world to receive a groundbreaking experimental gene therapy delivered straight into the brain, at Schneider Children’s Medical Center. The baby had suffered from severe epilepsy that did not respond to medication, caused by a rare genetic defect; a month after the injection, the seizures had not returned. It must be stressed at the outset that this is a single, experimental case, using a treatment that has not been approved for standard use, and it is still too early to draw conclusions. So reports the news site ynet.
The first signs
“He’s our youngest, born after three healthy children,” the baby’s father recounts. “It was a natural, easy birth at a normal weight, so we came home with a baby we thought was perfectly healthy.” At six weeks old, the infant began to have seizures. His parents rushed him to Schneider, where he underwent imaging and blood tests, but as no cause was found he was discharged. Within two weeks the seizures returned, and a significant developmental delay was diagnosed alongside them.
The diagnosis: a defect in the WWOX gene
Dr. Naama Orenstein, head of the genetics unit at Schneider, suspected the seizures stemmed from a defect in a gene called WWOX — a gene whose malfunction causes drug-resistant epilepsy, an abnormal head circumference, severe developmental delay, and vision damage resulting from degeneration of the brain. “I first encountered this gene in 2019,” she says. “In severe cases, the children do not survive beyond the age of four.” The defect is most common among Israelis of Yemenite descent.
Three years ago, a baby girl arrived at Schneider with movement and vocal-cord problems and an unusually small head circumference; genetic sequencing confirmed she had the syndrome, and she died at one year and seven months before a treatment could be found. In the wake of her death, Dr. Orenstein persuaded the Ministry of Health to include a genetic test for parents before pregnancy, to detect carriers of the syndrome in advance.
The gene that fights cancer — and protects the brain
In adults, the WWOX gene’s main roles are to regulate metabolism, maintain the integrity of the nervous system, and restrain cancerous tumors; its absence has been linked to various cancers. But when Prof. Rami Aqeilan, a researcher at the Lautenberg Center for Immunology and Cancer Research at the Hebrew University Faculty of Medicine, studied mice lacking the gene in their brains, he found that its absence impaired brain development and produced a severe disease resembling childhood epilepsy, along with vision problems, autism and balance disorders.
“The big breakthrough came when I injected a healthy copy of the gene directly into the brain of a sick mouse. We didn’t really believe it would stop the seizures — but it did,” he says. To study the disease further, his team took white blood cells from patients, “reprogrammed” them into a stem-cell-like state, and guided them to differentiate into brain cells grown in three dimensions — “a mini-brain in a lab dish” in which the treatment could be tested before being tried in a human.
From patent to medicine
Once the approach was established, Prof. Aqeilan sold the patent to the American company Mahzi Therapeutics, which develops brain-injected gene therapies for rare neurodevelopmental diseases. The company’s CEO, Dr. Yael Weiss — an Israeli running the company from California — took up the challenge. The gene was cloned in a laboratory in Israel and inserted into a virus that serves as a carrier, penetrating brain cells and prompting them to produce the healthy protein the patient is missing; the resulting liquid drug was flown, frozen, to Schneider.
The central obstacle: the drug has not yet been approved by the U.S. Food and Drug Administration (FDA). The solution was to administer it under “compassionate use,” which required — in an unprecedented regulatory race — approvals from the Helsinki Committee, the Ministry of Health, and international regulators.
The injection into the brain
The injection was performed by Dr. Ido Ben Zvi, a senior pediatric neurosurgeon and head of Schneider’s innovation center. The baby was anesthetized, and through an incision no larger than two centimeters the drug was introduced into the cisterna magna — the large space around the brain that holds cerebrospinal fluid. Four milliliters were injected slowly over four minutes.
“The drug had never been tested in humans, so its side effects were unknown. One of the risks was that the baby would go into anaphylactic shock and die on the operating table. I felt I was holding the baby’s life in my hand.” — Dr. Ido Ben Zvi, pediatric neurosurgeon, Schneider
What comes next
Since the injection, the seizures have not returned, and doctors in Israel and abroad are following the baby’s progress closely. “It’s too early to declare eureka,” Prof. Aqeilan cautions, “but I hope I have managed to bring a cure to these children — or at least to prolong their lives and improve their quality.” This is an early stage, with a single patient and short follow-up; it will take considerable time to know whether the treatment is safe and effective over the long term, and whether it will become available in the future.
