Genetic research team at UPenn set to progress gene therapy contender for Angelman syndrome

A promising development is underway in the fight against Angelman syndrome, as the Foundation for Angelman Syndrome Therapeutics (FAST) and the University of Pennsylvania continue their collaboration to advance a gene therapy for this genetic disorder.

The gene therapy, being developed by FAST's GeneTx, targets the molecule that keeps the paternal UBE3A gene inactive in certain brain regions. In Angelman syndrome, only the maternal UBE3A gene copy is active, while the one inherited from the father is turned off. If the maternal UBE3A gene is dysfunctional, brain cells lack instructions provided by the gene, leading to the disease's symptoms, such as developmental delay, motor impairment, communication issues, and seizures.

The experimental therapy, GTX-102, is designed to restore or compensate for the defective or missing UBE3A gene expression on chromosome 15. The gene therapy will be delivered directly into the central nervous system (CNS) using a harmless adeno-associated virus (AAV).

The Phase 1/2 clinical trial for GTX-102 is currently ongoing at multiple sites in the U.S., with recruitment continuing. The trial (NCT04259281) is evaluating the safety and tolerability of GTX-102 by injection into the spine in children ages 4-17 with Angelman syndrome.

FAST's chief science officer, Allyson Berent, stated that it is their goal to ensure that excellent science is always advanced as safely and efficiently as possible. The gene therapy program's director, Jim Wilson, added that the collaboration aims to advance a promising candidate to clinical trials.

The development of this gene therapy for Angelman syndrome addresses a high clinical unmet need associated with the disorder. FAST has been sponsoring preclinical research at the University of Pennsylvania's Gene Therapy Program since 2017, and the organisation supports research with the goal of promoting treatments that could be used in clinical practice.

Preclinical data supports advancing a human clinical candidate for Angelman syndrome, and if successful, GTX-102 could potentially benefit those living with the condition. The gene therapy aims to either introduce a healthy copy of the UBE3A gene into nerve cells or reactivate the paternal copy, offering hope for individuals and families affected by Angelman syndrome.

Genetic research team at UPenn set to progress gene therapy contender for Angelman syndrome