Gene Therapy Research Aims to Treat Angelman Syndrome

Researchers at UC Davis Health have made a significant stride in the treatment of Angelman syndrome, a rare neurodevelopmental disorder. A new gene therapy, currently in preclinical testing, aims to reduce or eliminate the condition’s symptoms by replacing a missing protein with a functional one. The research is being funded by a $4.5 million grant from the California Institute for Regenerative Medicine (CIRM).

The project is a collaboration between neuroscientist Jill Silverman and associate professor Joseph Anderson, who specializes in developing stem cell gene therapies. Angelman syndrome, which affects about 1 in 15,000 live births, is caused by the loss of the functional UBE3A gene, leading to impaired nervous system function and a range of symptoms including developmental delays, seizures, and speech challenges.

A Novel Approach for a Neurodevelopmental Condition

The innovative therapy works by modifying a patient’s own bone marrow blood stem cells to serve as a delivery vehicle for a functional version of the UBE3A gene. According to Anderson, the therapy essentially uses the patient’s “immune system as a delivery vehicle” to get the therapeutic protein to the brain. This approach, which has been successful in treating other diseases, has never before been used for a neurodevelopmental condition.

In an initial study published in 2021, the researchers demonstrated that the therapy successfully reversed symptoms of Angelman syndrome in adult mouse models and prevented them in very young mouse models. This finding was a major breakthrough, as it contradicted the previous belief that the condition’s symptoms could not be reversed beyond early childhood.

Advancing to Clinical Trials

The current research focuses on ensuring the therapy’s safety as the team prepares to move it into human clinical trials. A key part of this work involves finding the precise balance of the UBE3A protein—too little causes Angelman syndrome, while too much can lead to another neurodevelopmental condition, Dup15q syndrome.

“This is a Goldilocks situation,” Silverman explained. “We need just the right amount of the protein.”

The researchers believe that if successful, this gene therapy approach could be expanded to treat other neurodevelopmental conditions, offering new hope for patients and families.