Genetics and Therapeutic Overview

Quick Overview

In this presentation, Allyson Berent, Chief Science Officer for FAST, provides an overview of the genetics behind Angelman Syndrome and the current research being done to develop therapeutics for the condition. She discusses different strategies, such as gene replacement therapy, antisense oligonucleotides, artificial transcription factors, and CRISPR technology, that are being explored by various pharmaceutical companies. Berent emphasizes the importance of understanding the risks and benefits of these therapies and encourages parents to consult with their physicians and read the patient consent forms before participating in clinical trials. She also highlights the collaborative efforts of the Angelman Syndrome Biomarker and Outcome Measure Consortium in sharing data and developing assessments for measuring treatment outcomes. Berent concludes by expressing hope for the future and the potential for significant advancements in the treatment of Angelman Syndrome.


In this talk, I will provide a high-level overview of the genetics behind Angelman Syndrome and the current research being conducted to develop therapeutics for the disorder. I will also discuss the roadmap to meaningful therapeutics and the collaborative efforts of various pharmaceutical companies in this field.

Understanding Angelman Syndrome

Angelman Syndrome is caused by the loss of function of a single gene called UBE3A, which is vital for brain function. The UBE3A gene codes for a protein that plays a crucial role in speech, movement, and learning. In individuals with Angelman Syndrome, the maternal copy of the UBE3A gene is either missing or non-functional, while the paternal copy is present but silenced. This phenomenon, known as genomic imprinting, affects approximately 1% of our genome.

Therapeutic Strategies

Gene Replacement Therapy

One approach to treating Angelman Syndrome is gene replacement therapy, which involves delivering a functional UBE3A gene into neurons using a viral delivery system. Several pharmaceutical companies are actively pursuing this strategy, including Amicus, PTC Therapeutics, UC Davis, and Sarepta.

Activating the Paternal Copy

Another strategy is to activate the paternal copy of the UBE3A gene. This can be achieved through antisense oligonucleotides (ASOs), artificial transcription factors (ATFs), or CRISPR technology. Biogen, Ionis, Roche, Genentech, and UC Davis are among the companies working on these approaches.

Downstream Therapeutics

In addition to gene-based therapies, there are also downstream therapeutic strategies being explored. These include GABA replacement therapy, ketone supplements, and compounds that improve communication between neurons. Ovid Therapeutics, Disruptive Nutrition, Neuren, and NYU are among the companies working on these approaches.

Clinical Trial Readiness

To prepare for clinical trials, efforts are underway to develop outcome measures and biomarkers specific to Angelman Syndrome. The Angelman Syndrome Biomarker and Outcome Measure Consortium is a collaborative effort between pharmaceutical companies, foundations, and academic researchers to develop assessments for children with Angelman Syndrome. The Global Angelman Syndrome Registry is also collecting data to support clinical trial readiness.


The field of Angelman Syndrome research is rapidly advancing, with multiple therapeutic strategies being explored. Collaboration between pharmaceutical companies, researchers, and the Angelman community is crucial for the development of effective treatments. Parents are encouraged to stay informed, participate in registries and studies, and consult with healthcare professionals to make informed decisions about potential clinical trials for their children.

Talk details

  • Title: Genetics and Therapeutic Overview
  • Author(s): Allyson Berent
  • Author(s)’ affiliation: FAST
  • Publication date: 2019-12-27
  • Collection: 2019 FAST Science Summit