Global Game-Changer: Sheba Medical Center Develops a Personalized Genetic Drug for an 8-Year-Old Girl with a Rare Neurodevelopmental Disorder

RAMAT GAN, Israel – November 4, 2025 – A multidisciplinary team of researchers and physicians at Sheba Medical Center has developed a personalized RNA-based therapy for an 8-year-old patient suffering from a rare neurodevelopmental disorder caused by a mutation in the GNAO1gene. This marks the first time in Israel—and one of the few instances worldwide—where a customized genetic drug has been created specifically for a patient, designed to precisely modulate the expression of the defective gene.

The disorder, known as GNAO1-neurodevelopmental disorder, causes severe developmental delays, involuntary movements, and sometimes seizures. Until now, there has been no available drug treatment for the disease, only symptomatic therapies.

The drug developed at Sheba is based on Antisense Oligonucleotide (ASO) technology—short nucleic acid molecules capable of “silencing” the defective and toxic copy of the gene, thereby restoring cellular balance. The researchers created a library of dozens of different ASO molecules, testing their effectiveness and specific impact in cell models derived from the patient. Ultimately, they identified one ASO molecule with a specific sequence that successfully reduced expression of the defective gene and restored normal neuronal function.

In laboratory experiments conducted on nerve cells generated from the patient’s skin biopsy, a reduction of up to 75% in the defective gene’s expression was recorded, alongside improvements in molecular and functional markers. To further assess clinical potential, a genetic animal model replicating the patient’s condition was developed, which also demonstrated similar improvements in function.

The drug was manufactured according to GMP standards and underwent extensive toxicity testing, showing a strong safety profile. Following approval by Israel’s Ministry of Health under the compassionate use program, the patient received the first dose of treatment this week.

Dr. Dan Dominissini, Head of Sheba’s Diagnostic Division and Deputy Director of the Research Authority, stated,“The ability to develop a personalized drug tailored to a patient’s genetic sequence within a world-leading medical center, and in such a short time, reflects the revolution currently transforming medicine. RNA is at the heart of next-generation precision medicine, and Sheba is placing Israel at the forefront of this field.”

Prof. Bruria Ben-Zeev, former Director of the Pediatric Neurology Unit at the Edmond and Lily Safra Children’s Hospital and current Medical Director of the RNA Therapy Program, added,
“For the child and her family, this represents a tangible hope for improved daily functioning and quality of life. We anticipate that in the future, this approach will be expanded to help additional children with rare diseases for which no treatments currently exist.”

The development team from Sheba included Dr. Dan Dominissini, Head of the Diagnostic Division and Deputy Director of the Research Authority; Dr. Nofer Mor, Head of the RNA Therapy Research Group; Prof. Gidi Rechavi, Director of the Cancer Research Center; and Prof. Bruria Ben-Zeev, together with a multidisciplinary team of leading researchers and physicians.