University of Pennsylvania scientists accelerate progress towards using gene therapy on Angelman syndrome with their research team.

The Foundation for Angelman Syndrome Therapeutics (FAST) and the University of Pennsylvania's Gene Therapy Program have been collaborating since 2017 to develop a promising gene therapy for Angelman syndrome. This condition, characterised by developmental delay, motor impairment, communication issues, and seizures, has a significant clinical unmet need.

The gene therapy, designated as GTX-102, is designed to improve developmental symptoms by targeting the genetic cause across different genotypes and age groups. Preclinical data supports the advancement of this human clinical candidate, potentially leading to an investigational new drug application for first-in-human clinical trials.

GTX-102 is unique in its approach, as it targets the genetic cause of Angelman syndrome, which is the absence or malfunction of the ubiquitin protein ligase E3A (UBE3A) gene. In certain brain regions, only the gene copy inherited from the mother is active, while the gene copy 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 symptoms of Angelman syndrome.

The experimental therapy will be delivered directly into the central nervous system (CNS) using a harmless adeno-associated virus (AAV). This delivery method ensures that the healthy copy of the UBE3A gene reaches the intended target, providing the necessary instructions to the brain cells.

FAST's chief science officer, Allyson Berent, stated that it is their job to ensure that excellent science is always advanced as safely and efficiently as possible, and to seize every opportunity to potentially benefit those living with Angelman syndrome. FAST has started GeneTx, which developed the experimental therapy GTX-102 that targets and blocks the molecule keeping the paternal copy of the UBE3A gene inactive.

Jim Wilson, MD, PhD, director of the Gene Therapy Program, stated that the partnership has chosen a promising human clinical candidate to advance the gene therapy for Angelman syndrome quickly and safely. The Phase 1/2 clinical trial (NCT04259281) is currently underway, evaluating the safety and tolerability of GTX-102 by injection into the spine in children ages 4-17 with Angelman syndrome. Recruitment for this trial is ongoing at multiple sites in the U.S.

FAST has been sponsoring preclinical research at the Gene Therapy Program at the University of Pennsylvania since 2017 to develop this groundbreaking gene therapy. The organisation supports research with the goal of promoting treatments that could be used in clinical practice. If the ongoing clinical trials are successful, GTX-102 could pave the way for a new era in the treatment of Angelman syndrome.

University of Pennsylvania scientists accelerate progress towards using gene therapy on Angelman syndrome with their research team.