FAST Roadmap to a C.U.R.E. 2.0

Quick Overview

Allyson Berent, Chief Science Officer for the Foundation for Angelman Syndrome Therapeutics (FAST), gave a talk at the 2022 FAST Science Summit about the progress and future directions in Angelman Syndrome research. She emphasized the importance of understanding the science behind the disorder and encouraged attendees to become advocates for their children and the Angelman Syndrome community. Berent discussed the four pillars of research: gene therapy, unsilencing the paternal copy of the gene, addressing synapse dysfunction, and accelerating drug development. She highlighted the progress made in each of these areas and the ongoing clinical trials for potential treatments. Berent also announced the launch of the first FAST Center for Translational Research at Rush University, which aims to train clinical trialists and improve the efficiency of clinical trial enrollment. She concluded by urging attendees to become fundraisers, advocates, and ambassadors for Angelman Syndrome research.

Welcome to the 2022 FAST Science Summit! I am Allyson Berent, the Chief Science Officer for the Foundation for Angelman Syndrome Therapeutics (FAST). In this talk, I will be discussing our roadmap to a C.U.R.E. 2.0 for Angelman Syndrome and the importance of understanding the science behind it.

Introduction

As a veterinarian, clinician, and clinical trialist, my career has focused on finding treatments for naturally occurring diseases in animals. However, my most important role is being a mother to three beautiful girls, one of whom, Quincy, lives with Angelman Syndrome. In this talk, I aim to simplify the complex science behind Angelman Syndrome and empower you to become an advocate for your child and our community.

The Basics of Angelman Syndrome

Angelman Syndrome is caused by a missing or non-functional copy of a single gene on chromosome 15. This gene, called UBE3A, is responsible for regulating proteins in the brain and maintaining the balance between excitatory and inhibitory neurotransmitters. Without UBE3A, individuals with Angelman Syndrome experience symptoms such as speech impairment, seizures, coordination difficulties, and sleep disturbances.

The Four Pillars of our Roadmap

Our roadmap to a C.U.R.E. 2.0 for Angelman Syndrome is built on four pillars:

1. Gene Therapy: Replacing the missing or non-functional UBE3A gene or protein.
2. Unsilencing: Activating the paternal copy of the UBE3A gene.
3. Downstream Targeting: Addressing the synapse and related neurotransmitter imbalances.
4. Accelerating: Preparing for clinical trials and drug approvals.

Advances in Gene Therapy

Gene therapy offers promising possibilities for treating Angelman Syndrome. Researchers have explored various methods, including adeno-associated viruses, lentiviruses, and enzyme replacement therapy, to deliver the missing UBE3A gene or protein into the brain. Clinical trials are currently underway to test the safety and efficacy of these approaches.

Unsilencing the Paternal Copy

Another avenue of research focuses on unsilencing the paternal copy of the UBE3A gene. This can be achieved through antisense oligonucleotides (ASOs), artificial transcription factors, or CRISPR gene editing. These methods aim to reduce the expression of the antisense transcript that silences the paternal copy, allowing the gene to be read and produce UBE3A protein.

Downstream Targeting

Addressing the synapse and neurotransmitter imbalances is crucial for improving the symptoms of Angelman Syndrome. Researchers are exploring drugs that target GABA receptors, ketone esters, IGF-1 agonist ligands, and BDNF analogs to restore the balance between excitatory and inhibitory neurotransmitters.

Accelerating Drug Development

To accelerate drug development for Angelman Syndrome, we need to train clinical trialists, improve infrastructure, and create specialized centers for interventional therapies. These centers will focus on efficiently enrolling patients in clinical trials and delivering novel therapies. We also need to advocate for policy changes and raise awareness about Angelman Syndrome.

Join the Movement

You can make a difference in the fight against Angelman Syndrome by becoming an ambassador for science, fundraising, and advocating for policy changes. Together, we can support research, accelerate drug development, and improve the lives of individuals with Angelman Syndrome.

In conclusion, our roadmap to a C.U.R.E. 2.0 for Angelman Syndrome is built on the pillars of gene therapy, unsilencing, downstream targeting, and accelerating drug development. With ongoing research and the support of our community, we are confident that we will find effective treatments for Angelman Syndrome.