Therapeutics 101 with Allyson Berent

Quick Overview

In this talk, Allyson Berent discusses the different therapeutic options for Angelman Syndrome. She explains that there are three main approaches: gene therapy, activating the paternal allele, and downstream therapeutics. Gene therapy involves replacing the missing UBE3A gene or protein in the brain using a virus vector. Activating the paternal allele involves turning on the father’s copy of the gene using artificial transcription factors or antisense oligonucleotides. Downstream therapeutics focus on treating the symptoms of Angelman Syndrome, such as GABA replacement therapy or ketone esters. Berent also explains the process of bringing therapeutics to humans, including the different phases of clinical trials. She emphasizes the importance of outcome measures to prove the efficacy of treatments. Berent concludes by expressing gratitude to the researchers, pharmaceutical companies, and organizations that are working towards finding a cure for Angelman Syndrome.


In this talk, Allyson Berent, the Chief Scientific Officer at FAST, provides an overview of the basics of science and therapeutics for Angelman Syndrome. She emphasizes the importance of understanding the science behind the condition and the potential treatments in order to make informed decisions for individuals with Angelman Syndrome.

The Basics of Angelman Syndrome

Berent explains that Angelman Syndrome is caused by a reduction in the expression of the UBE3A gene, which is located on chromosome 15. This gene is responsible for controlling various functions of the brain, such as speech, movement, learning, and memory. When the UBE3A gene is not functioning properly, individuals with Angelman Syndrome experience symptoms such as poor balance, lack of speech, seizures, poor sleep, anxiety, dyspraxia, and poor attention spans.

Therapeutic Approaches

Berent discusses three main therapeutic approaches for Angelman Syndrome:

  1. Gene Therapy: This approach involves replacing the missing UBE3A gene or protein in the brain. Clinical trials for gene therapy have already been conducted for other neurogenetic disorders, and the results have been promising. Researchers are currently working on finding the ideal candidate for the gene, the best delivery method, and the most effective virus vector to ensure widespread distribution in the brain.

  2. Activating the Paternal Allele: The paternal copy of the UBE3A gene is silenced in individuals with Angelman Syndrome. This approach aims to activate the paternal allele to restore UBE3A expression. Researchers have successfully used antisense oligonucleotides (ASOs) and artificial transcription factors (ATFs) to activate the paternal allele in animal models. Clinical trials for ASOs have already shown success in humans with other genetic disorders.

  3. Downstream Therapeutics: This approach focuses on treating the symptoms of Angelman Syndrome by targeting the downstream effects of UBE3A deficiency. Examples include GABA replacement therapy, anti-epileptic drugs, sleep aids, and ketone esters. These treatments aim to improve motor function, sleep, learning, memory, and reduce seizures.

Progress and Challenges

Berent highlights the progress that has been made in the field of Angelman Syndrome therapeutics. Gene therapy has already been successful in animal models, and clinical trials for other neurogenetic disorders have shown positive results. Activating the paternal allele and downstream therapeutics are also showing promise.

However, Berent acknowledges that there is still work to be done. Researchers need to continue refining the therapeutic approaches, conducting preclinical studies, and demonstrating safety and efficacy in humans. Additionally, outcome measures and biomarkers need to be developed to objectively assess the effectiveness of treatments.


Berent concludes by emphasizing the importance of knowledge and understanding for individuals and families affected by Angelman Syndrome. She expresses gratitude to the researchers, pharmaceutical companies, and organizations that are dedicated to finding a cure for Angelman Syndrome. Berent encourages individuals to stay informed, ask questions, and be advocates for their loved ones with Angelman Syndrome.

Talk details

  • Title: Therapeutics 101 with Allyson Berent
  • Author(s): Allyson Berent
  • Author(s)’ affiliation: FAST
  • Publication date: 2016-12-02
  • Collection: 2016 FAST Science Summit