Therapeutic Strategies for the Treatment of Angelman Syndrome

Quick Overview

In this presentation, Allyson Berent discusses the current landscape of therapeutic strategies for the treatment of Angelman syndrome. She highlights the importance of understanding the genetics of Angelman syndrome and how it relates to potential therapeutic approaches. Berent discusses various strategies, including gene replacement therapy, paternal activation, and downstream targets. She also emphasizes the need for clinical trials and the importance of caregiver input in the development of meaningful endpoints. Berent concludes by encouraging participation in research studies and clinical trials and expressing optimism for the future of Angelman syndrome treatment.

Introduction

In this talk, we will explore the latest updates in the research stage of Angelman Syndrome and discuss the therapeutic strategies being developed for its treatment. Understanding the basics of Angelman Syndrome genetics is crucial in comprehending the therapeutic strategies being proposed. This talk aims to provide an overview of Angelman Syndrome, its genetics, and the current landscape of therapeutic treatments.

About the Author

Allyson Berent is the Chief Science Officer for the Foundation for Angelman Syndrome Therapeutics and a physician specializing in clinical research. With her expertise in clinical trial design and development, she plays a crucial role in translating medical device development into potential therapeutic treatments for pediatrics.

Therapeutic Strategies

Gene Replacement Therapy

Gene replacement therapy involves using viral vectors, such as adeno-associated viruses (AAV), to deliver a functional copy of the UBE3A gene into the brain and spinal cord. This therapy aims to replace the missing or non-functioning UBE3A gene in individuals with Angelman Syndrome. Several gene replacement therapy programs are currently being developed and tested in preclinical and clinical trials.

Paternal Activation

Paternal activation strategies focus on activating the silent paternal copy of the UBE3A gene in neurons. This can be achieved through various approaches, including antisense oligonucleotides (ASOs), artificial transcription factors (ATFs), CRISPR technology, and short hairpin RNA (shRNA). These strategies aim to unsilence the paternal copy of the gene and restore UBE3A protein production.

Downstream Targets

In addition to gene replacement therapy and paternal activation, researchers are also exploring downstream targets for therapeutic intervention. These targets include GABA agonists, ketone supplements, IGF-1 and IGF-2 ligands, and anti-inflammatory neuronal stem cells. These targets aim to address the synaptopathy and other symptoms associated with Angelman Syndrome.

Progress and Clinical Trials

Over the past few years, significant progress has been made in the development of therapeutic strategies for Angelman Syndrome. Multiple programs have moved from basic research to preclinical and clinical trial stages. Currently, there are several programs in IND-enabling studies or clinical trials, including gene therapy, stem cell therapy, ASOs, ATFs, CRISPR, and downstream targets.

Participating in Research

Parents and caregivers can actively participate in research and clinical trials to contribute to the development of therapeutic treatments for Angelman Syndrome. Participation can involve joining the Global Angelman Syndrome Registry, participating in endpoint development studies, and discussing trial participation with doctors.

Conclusion

The landscape of therapeutic strategies for Angelman Syndrome is rapidly evolving, with multiple programs in various stages of development. Knowledge and understanding of these strategies empower parents and caregivers to make informed decisions for their children. By actively participating in research and clinical trials, the Angelman Syndrome community can contribute to the development of effective treatments and celebrate the hope for a better future for individuals with Angelman Syndrome.

This talk is based on a presentation by Allyson Berent at the 2020 FAST Science Summit.