Research Panel Q&A: Insights from the 2024 ASF Family Conference

Quick Overview

The research panel at the ASF Family Conference discussed the current state and future of Angelman Syndrome research. The panel, moderated by Dan Harvey, included experts like Mark Zylka, Ype Elgersma, and Ryan Butler, who shared insights into various research approaches, including ASOs, gene therapies, and small molecules. They highlighted the potential of genome editors like CRISPR-Cas for permanent solutions, while acknowledging the challenges of delivery to the brain due to the blood-brain barrier. The panel emphasised the importance of safety and efficacy testing in animal models before human trials. They also discussed the role of patient advocacy in supporting research and the necessity of animal research for progress. The session concluded with a call for continued advocacy and support from families and patient groups to drive research forward.

The 2024 ASF Family Conference hosted a compelling Research Panel Q&A session, moderated by Dan Harvey, a long-time board member and collaborator with the Scientific Advisory Committee. The session aimed to provide an interactive platform for discussing the current state and future directions of research in Angelman Syndrome, with a focus on non-clinical aspects such as gene therapies and small molecule research.

Panel Introduction and Background

The panel featured prominent researchers including Mark Zylka, Ype Elgersma, and Ryan Butler, who shared their journeys into Angelman Syndrome research. Mark Zylka from the University of North Carolina at Chapel Hill recounted his collaboration with Ben Philpot, which began over 20 years ago. Their work initially focused on receptors regulating brain excitability, eventually leading to groundbreaking research on the UBE3A gene associated with Angelman Syndrome. Zylka highlighted the serendipitous discovery of topoisomerase inhibitors, which, despite their side effects, demonstrated the potential to activate the paternal copy of UBE3A.

Ype Elgersma from Erasmus Medical Center in Rotterdam shared his 25-year journey studying the UBE3A protein and its implications in Angelman Syndrome. His work has been pivotal in understanding the disorder’s molecular underpinnings and developing potential therapeutic strategies.

Ryan Butler, who began his work in gene therapy at UNC Chapel Hill, emphasised the importance of meeting families affected by Angelman Syndrome, which has been a driving force in his research efforts. His work focuses on developing gene therapy approaches to permanently activate the paternal allele of UBE3A.

Exploring Treatment Approaches

The panel delved into various treatment approaches beyond antisense oligonucleotides (ASOs), which are currently in clinical trials. Mark Zylka discussed the potential of genome editors like CRISPR-Cas to permanently modify the genome and activate the paternal UBE3A gene. However, he cautioned about the higher safety risks associated with permanent genome modifications compared to the reversible nature of ASOs.

Ryan Butler highlighted the exploration of novel viral capsids for gene therapy, which could improve distribution in the brain and enhance treatment efficacy. He also discussed the challenges of ensuring safety and efficacy in animal models before transitioning to human trials.

Ype Elgersma reminded the audience of the ongoing need for symptom-alleviating treatments, such as improved anti-epileptic drugs, which remain crucial until a definitive cure is found.

Safety and Efficacy Considerations

The panel addressed the rigorous safety evaluations required for these innovative therapies. Ryan Butler outlined the comprehensive testing protocols, including neurocognitive assessments and toxicity studies, to ensure the safety of gene therapies. The importance of non-human primate studies as a next step in safety evaluation was also noted.

The Role of Patient Advocacy and Family Support

The session concluded with a discussion on the vital role of patient advocacy groups and families in supporting research efforts. The panel emphasised the importance of advocacy for increased research funding, particularly at the federal level, to advance Angelman Syndrome research. They also highlighted the critical role of seed funding from organisations like the Angelman Syndrome Foundation in enabling foundational research that can attract larger grants.

Families were encouraged to continue their advocacy and support, as their perseverance and engagement are crucial in driving research forward. The panel acknowledged the challenges faced by families and expressed gratitude for their inspiration and support.

In summary, the Research Panel Q&A at the 2024 ASF Family Conference provided valuable insights into the current research landscape for Angelman Syndrome. The session highlighted the collaborative efforts of researchers, the importance of innovative treatment approaches, and the critical role of patient advocacy in advancing research and ultimately improving outcomes for individuals with Angelman Syndrome.