Gene Therapy Round Table: Ask the Experts

Quick Overview

The Gene Therapy Round Table is a platform where experts discuss gene therapy for Angelman Syndrome. The panelists, who are researchers, are working on different strategies for gene therapy and gene editing, including gene replacement, gene secreted protein replacement, antisense transcript, zinc finger, and hematopoietic stem cell gene therapy approaches. They believe gene therapy could benefit all ages, but earlier treatment may lead to better outcomes. Challenges include determining the best combination of components and route of administration for their therapies. They are also considering different dosages and routes of administration in clinical trials. The panelists are aware of the challenges and regulations involved in clinical trials, including the need to start with adult populations. They are also considering the potential for pediatric populations in clinical trials. The affordability and accessibility of gene therapy for Angelman syndrome will depend on various factors, including pricing structures and societal efforts. The Angelman syndrome community’s support and involvement are crucial for advancing research in this field.

Introduction

The Gene Therapy Round Table is a platform where experts in the field of gene therapy, gene editing, and viral vector delivery come together to answer questions about Angelman Syndrome. In this talk, we will summarize the key points discussed during the round table.

Question and Answer Format

The round table follows a question and answer format, with questions submitted in advance by the community. Over 50 questions were received, many of which were similar.

Panelists and Focus

The panelists are researchers, not pharmaceutical or biotech companies. They are not competing with each other but are focused on finding the best treatment for Angelman Syndrome. While they may not be able to answer questions about pricing or specific company agendas, their expertise lies in gene therapy, gene editing, and viral vector delivery.

Strategies and Approaches

The panelists are working on different strategies for gene therapy and gene editing. These include gene replacement, gene secreted protein replacement, antisense transcript, zinc finger, and hematopoietic stem cell gene therapy approaches. They believe that Angelman Syndrome is appealing for gene therapy strategies due to its monogenic nature and the unique opportunity to target the silenced allele.

Treatment Potential and Timing

The panelists believe that gene therapy has the potential to benefit all ages, but earlier treatment may lead to better outcomes. They are working towards Phase 1 clinical trials for their specific strategies.

Challenges and Considerations

The panelists face challenges in determining the best combination of components and route of administration for their therapies. They are optimistic about the potential for therapeutic benefits but acknowledge that the extent of improvement is uncertain. They are considering different dosages and routes of administration in clinical trials.

Clinical Trials and Regulatory Considerations

The panelists are aware of the challenges and regulations involved in clinical trials, including the need to start with adult populations. They are also considering the potential for pediatric populations in clinical trials, but this may require further negotiation with regulatory agencies. They emphasize the need for robust outcome measures and the potential for quicker results in younger populations.

Brain Delivery and Expression

The panelists are considering the potential for high transfection and gene expression in the human brain with viral vectors. They are aware of the potential for immune privilege in spinal fluid delivery, allowing for potential re-administration of the therapy. They also acknowledge that different therapies may have different distribution and expression levels in the brain.

Technology Limitations and Safety

The panelists are aware of the challenges and limitations of different gene therapy and gene editing technologies, such as CRISPR-Cas9. They are working towards Phase 1 clinical trials and face challenges in demonstrating safety and efficacy. They are considering the potential for permanent or long-lasting effects with different treatment options. They also acknowledge that some treatments may require multiple administrations, similar to other drugs.

Gene Activation and Vectors

Different strategies are being explored for activating specific genes. Adenovirus, adeno-associated virus, and lentivirus are all engineered viruses used as vectors in gene therapy. Adeno-associated virus is preferred for targeting non-dividing cells like neurons. Gene therapy using adeno-associated virus may have some immune toxicity, but it is less than other viral vectors. Preclinical studies are necessary to assess the potential risks and side effects of gene therapy and delivery methods.

Risks and Considerations

Children with Angelman syndrome are not expected to have a higher risk of adverse immune reactions with viral vectors. Trials on pigs for Angelman syndrome gene therapy have not been conducted yet. Preclinical studies and preparation for clinical trials take time due to the need for thorough testing and evaluation. The differences in skill sets among individuals with the same genetic mutation can be influenced by genetic background and other factors. Overexpression of the UBE3A gene may have potential risks, but the location and method of gene activation can minimize those risks.

Affordability and Accessibility

The affordability and accessibility of gene therapy for Angelman syndrome will depend on various factors, including pricing structures and societal efforts. The approval and availability of Spinraza for spinal muscular atrophy may provide insights into insurance coverage and accessibility for gene therapies.

Community Support and Involvement

The Angelman syndrome community’s support and enthusiasm are greatly appreciated by the researchers and scientists. The power and impact of the community’s involvement in research and clinical studies should not be underestimated. Parent and child participation in registries and clinical studies is crucial for advancing research and understanding the disease. Transparency in scientific findings and potential detours in the research process are important for progress in gene therapy for Angelman syndrome.

In conclusion, the Gene Therapy Round Table provides a valuable platform for experts to discuss and answer questions about gene therapy for Angelman Syndrome. The panelists are working on different strategies and approaches, facing challenges and considering various factors for successful clinical trials and treatment options. The support and involvement of the Angelman syndrome community are crucial for advancing research in this field.

Talk details

  • Title: Gene therapy round table: ask the experts
  • Author(s): Arthur Beaudet, Scott Dindot, Kevin Nash, David Segal, Edwin Weeber, Jim Wilson, Ashley Winslow
  • Author(s)’ affiliation: Baylor College of Medicine; Texas A&M University; University of South Florida; University of California, Davis; Penn Medicine’s Orphan Disease Center
  • Publication date: 2017-12-22
  • Collection: 2017 FAST Science Summit