GTX-102 Phase 1/2 Clinical Trial Update: Development of an ASO for Angelman Syndrome

Quick Overview

This summary provides an update on the GTX-102 Phase 1/2 clinical trial for Angelman Syndrome. The trial involves the use of an investigational drug, an antisense oligonucleotide (ASO), to unsilence the paternal gene and increase protein production. The trial has experienced some safety issues, including transient ataxia and fatigue, as well as lower extremity weakness in some patients. The protocol has been amended to address these issues, with lower doses and a flush technique to minimize local toxicity. Preliminary results show improvements in communication, motor skills, and adaptive behavior, as measured by the Vineland scale and other assessments. EEG data also suggests a decrease in epileptiform discharges. Caregiver reports indicate improvements in spoken words, signs and gestures, and social engagement. The trial is ongoing, and further data will be collected to determine the effectiveness of the ASO strategy for Angelman Syndrome.


In this talk, we provide an update on the GTX-102 Phase 1/2 clinical trial, which focuses on the development of an antisense oligonucleotide (ASO) for the treatment of Angelman syndrome. We discuss the trial protocol, safety concerns, preliminary results, and future directions.


GTX-102 is an investigational drug being developed by Genetics in collaboration with Ultragenyx. It is an ASO, which is a synthetic single strand of DNA and RNA that aims to unsilence the paternal gene responsible for producing the needed protein in individuals with Angelman syndrome.

Trial Overview

The trial is the first study in humans and involves four monthly doses administered through a lumbar puncture. The primary objective is to assess the safety of the drug, while secondary objectives include evaluating how the drug behaves in the body (pharmacokinetics) and exploring its effects on multiple functional domains in Angelman syndrome.

Protocol Amendment

The trial experienced safety issues related to lower extremity weakness in some patients. This led to a protocol amendment, which involved starting at lower doses, implementing smaller and less frequent dose escalations, and using a flush in Trendelenburg position to move the drug away from the lower back and towards the brain.

Preliminary Results

Preliminary results from the first five patients in the trial showed some safety concerns, including transient ataxia and fatigue after drug administration. However, these side effects were considered benign and resolved within a few days. Other adverse events, such as headaches and infections, were not directly related to the drug.

Despite the safety concerns, the trial demonstrated promising results in terms of clinical improvements. Patients showed increases in communication skills, motor function, adaptive behavior, and socialization. Objective measures, such as EEG and the Bayley and Vineland scales, also indicated positive changes in cognitive functioning and language skills.

Future Directions

The trial is ongoing, and enrollment is open at various sites in the United States, Canada, and the United Kingdom. The researchers plan to continue monitoring the safety and efficacy of GTX-102 in individuals with Angelman syndrome. They aim to assess the long-term effects of the drug and determine the optimal dosage and age range for treatment.


The GTX-102 Phase 1/2 clinical trial shows promise in the development of an ASO for Angelman syndrome. While safety concerns have been addressed through a protocol amendment, preliminary results indicate positive clinical improvements in multiple domains. Further research is needed to confirm these findings and determine the optimal treatment approach for individuals with Angelman syndrome.

This talk was written on behalf of Scott Stromatt and Elizabeth Berry-Kravis for the 2021 FAST Science Summit.

Talk details

  • Title: GTX-102 Phase 1/2 Clinical Trial Update, Development of an ASO for Angelman Syndrome: Science and Regulation
  • Author(s): Scott Stromatt, Elizabeth Berry-Kravis
  • Author(s)’ affiliation: GeneTx Biotherapeutics; Rush University Medical Center
  • Publication date: 2022-01-04
  • Collection: 2021 FAST Science Summit