Overview of the Therapeutic Landscape for Angelman Syndrome

Quick Overview

Allyson Berent, Chief Science Officer for the Foundation for Angelman Syndrome Therapeutics (FAST), gave a presentation at the 2021 FAST Science Summit. She discussed the therapeutic landscape for Angelman Syndrome and the progress being made in finding treatments and a potential cure for the disorder. Berent highlighted the importance of understanding the genetics behind Angelman Syndrome and the potential for gene therapy and gene editing to provide disease-modifying therapies. She also emphasized the need for collaboration, research, and clinical trials to advance treatment options. Berent introduced Jennifer Panagoulias and Lance Colwell, who have joined the FAST team to support drug development efforts. She concluded by encouraging the Angelman Syndrome community to continue working together to make a cure for the disorder a reality.

Introduction

In this talk, I will provide an overview of the current therapeutic landscape for Angelman Syndrome (AS). As the Chief Science Officer for the Foundation for Angelman Syndrome Therapeutics (FAST), I am dedicated to advancing research and finding transformative treatments for individuals with AS. I will discuss the genetics behind AS, the potential therapeutic approaches, and the importance of understanding these concepts for making informed decisions for individuals with AS.

Understanding Angelman Syndrome

Angelman Syndrome is a monogenetic disorder, meaning it is caused by a single gene mutation. The majority of individuals with AS are missing a gene called UBE3A, which is either completely absent or does not function properly. This gene is located on the 15th chromosome and is typically inherited from the mother. AS affects approximately 1 in 15,000 children worldwide, although the exact number is still being studied. It is important to note that AS is a non-degenerative disorder, meaning it does not worsen over time.

Therapeutic Approaches

Gene Replacement Therapy

One potential therapeutic approach is gene replacement therapy, which aims to replace the missing or non-functioning UBE3A gene. This can be done through adeno-associated virus (AAV) gene therapy or hematopoietic stem cell lentiviral gene therapy. Several companies and academic labs are currently working on gene replacement therapy for AS.

Paternal Gene Activation

Another approach is to activate the paternal copy of the UBE3A gene, which is normally silenced in neurons. This can be achieved through antisense oligonucleotides (ASOs), artificial transcription factors, CRISPR technology, or other methods. Multiple programs are currently exploring paternal gene activation for AS.

Downstream Targeting

Additionally, researchers are investigating downstream targets in the synapse, the junction between neurons, to improve communication and coordination. This includes testing drugs that target specific proteins involved in synaptic function.

Clinical Trial Readiness

In order to advance these potential therapies, it is crucial to be prepared for clinical trials. This involves creating animal models and cell lines for pre-clinical testing, developing biomarkers and outcome measures, and designing clinical trial protocols. The Foundation for Angelman Syndrome Therapeutics (FAST) is actively supporting these efforts through funding and collaboration.

The Roadmap for Success

FAST’s funding philosophy is focused on collaboration, understanding, readiness, and expediting drug development. By collaborating with families, scientists, pharmaceutical companies, and clinicians, FAST aims to accelerate the development of therapeutic candidates and move them towards clinical trials. The goal is to bring transformative treatments to individuals with AS, regardless of their age or genotype.

Conclusion

The therapeutic landscape for Angelman Syndrome is rapidly advancing, with multiple potential treatments in development. Through collaboration, understanding, and readiness, we are working towards the ultimate goal of finding a cure for AS. It is important for individuals and families affected by AS to stay informed and engaged in the research process, as knowledge is power in making decisions for their loved ones. Together, we can make the impossible possible and bring hope to the AS community.