FAST’s Roadmap to a Cure: A Year of Tough Setbacks and Huge Progress

Quick Overview

The Chief Science Officer for FAST, Allyson Brent, gave a presentation on FAST’s Roadmap to a Cure for Angelman Syndrome. She discussed the progress and setbacks in the past year, as well as the different pillars of their approach to finding a cure. The pillars include gene replacement therapy, activating the father’s copy of the gene, targeting the synapse, and preparing for clinical trials. Brent highlighted the importance of clinical trial readiness and the need for collaboration and funding to advance drug development. She also emphasized the potential of different therapeutic platforms and the commitment of FAST to continue their efforts until a cure is found.

Introduction

In this talk, I will be discussing FAST’s Roadmap to a Cure 2.0. As the Chief Science Officer for FAST, I am excited to share the progress we have made in the past year. We have faced setbacks, but we have also made significant strides towards finding a cure for Angelman Syndrome.

About FAST

FAST (Foundation for Angelman Syndrome Therapeutics) is a non-profit organization dedicated to funding research and finding a cure for Angelman Syndrome. We work closely with industry partners, academic researchers, and clinicians to develop meaningful and measurable endpoints for clinical trials.

The Journey So Far

Over the years, we have made significant progress in understanding Angelman Syndrome and developing potential treatments. We have come a long way, but there is still much work to be done. In this talk, I will provide an overview of the genetic basis of Angelman Syndrome and discuss the different approaches we are taking to find a cure.

Understanding Angelman Syndrome

Angelman Syndrome is a rare genetic disorder caused by a defect in chromosome 15. The causative gene, UBE3A, is responsible for the symptoms of Angelman Syndrome. Individuals with Angelman Syndrome have a range of symptoms, including a lack of speech, sleep issues, incoordination, and cognitive impairments.

Pillar 1: Gene Replacement Therapy

One approach we are exploring is gene replacement therapy, where we aim to replace the missing or defective UBE3A gene. This can be done using adeno-associated virus gene therapy, lentivirus hematopoietic stem cell gene therapy, or enzyme replacement therapy. These approaches have shown promise in animal models and are now being tested in clinical trials.

Pillar 2: Activating the Father’s Copy

Another approach is to activate the father’s copy of the UBE3A gene, which is naturally silenced in neurons. This can be done using antisense oligonucleotides (ASOs), zinc fingers, artificial transcription factors, CRISPR, or miRNA. These methods have shown success in animal models and are being further explored for their potential in treating Angelman Syndrome.

Pillar 3: Downstream Targeting

We are also investigating ways to target the synapse, the junction between neurons, to improve communication and reduce excitatory signals in the brain. This can be achieved through the use of compounds that enhance synaptic function.

Pillar 4: Clinical Trial Readiness

In order to advance drug development and ensure successful clinical trials, we are focusing on clinical trial readiness. This includes developing animal models, conducting natural history studies, establishing registries, and training clinical trialists. We are also working on newborn screening efforts to identify individuals with Angelman Syndrome early on.

The Challenges of Drug Development

Drug development is a complex and expensive process. It can take several years and millions of dollars to bring a drug from discovery to approval. However, we are committed to funding and supporting the development of potential treatments for Angelman Syndrome.

The Future of Angelman Syndrome Research

Looking ahead, we envision a future where there are multiple programs in the clinic and several drug approvals for Angelman Syndrome. We are focused on identifying gaps and accelerating all potential strategies to find a cure. We believe that with continued research and collaboration, we will be able to make a significant impact on the lives of individuals with Angelman Syndrome.

Conclusion

While there have been setbacks along the way, FAST remains dedicated to finding a cure for Angelman Syndrome. We are making progress in understanding the genetic basis of the disorder and developing potential treatments. With ongoing research and the support of the community, we are confident that we will achieve our goal of finding a cure for Angelman Syndrome.