Gene Therapy for Angelman Syndrome

Quick Overview

Dr. Jim Wilson, a pioneer in gene therapy, spoke at the 2018 FAST Science Summit about the potential of gene therapy for Angelman Syndrome. He discussed the use of viruses as delivery vehicles for introducing normal genes into cells to treat diseases at their root. Dr. Wilson highlighted the challenges of delivering genes to the brain and spinal cord, but expressed optimism about the progress being made. He emphasized the need for efficient gene delivery to a sufficient number of cells in order to be effective. Dr. Wilson concluded by proposing the “90-80 rule,” aiming for 80% gene transfer into neurons for successful clinical trials.

Introduction

In a recent talk at the 2018 FAST Science Summit, Dr. Jim Wilson discussed the potential of gene therapy for treating Angelman Syndrome, a rare neurogenetic disorder. Dr. Wilson shared his personal journey and the challenges he faced in developing a concept to treat rare diseases like Angelman Syndrome. He explained the use of viruses as delivery vehicles for gene therapy and the progress made in the field over the years.

The Power of Gene Therapy

Gene therapy involves introducing a normal version of a gene into cells to treat diseases at their root cause. Dr. Wilson emphasized the need for technical advancements to develop effective approaches for gene therapy. He highlighted the use of viruses, specifically adeno-associated viruses (AAVs), as a successful method for delivering therapeutic genes to cells.

Challenges and Progress

Dr. Wilson acknowledged the highs and lows that gene therapy has experienced over the years. Despite setbacks, he remained determined to move forward and work harder. He and his team focused on vector discovery, leading to the identification of a family of AAVs that showed promising results in model systems.

Gene Therapy for Angelman Syndrome

Dr. Wilson discussed the specific challenges of delivering genes to the central nervous system (CNS) for treating Angelman Syndrome. He explained that while gene transfer to the spinal cord is efficient, delivering genes to the brain is more challenging. He presented different methods, such as direct injection into the brain or infusion into the cerebral spinal fluid (CSF), and their potential for achieving widespread gene transfer.

Progress in Animal Models

Dr. Wilson shared the results of experiments conducted in animal models, including mice and dogs, to assess the effectiveness of gene transfer. He demonstrated successful gene expression in target areas of the brain and observed improvements in motor function and behavior in mice. He also discussed the use of AAV9, a vector that has shown promise in crossing the blood-brain barrier, in treating spinal muscular atrophy type 1.

The 90-80 Rule

Dr. Wilson proposed a new rule, the 90-80 rule, as a critical path to a successful clinical trial. He suggested that achieving 80% gene transfer into neurons in the CNS would greatly increase the likelihood of success. He expressed confidence in the potential of gene therapy for Angelman Syndrome and emphasized the need for further research and advancements in the field.

Conclusion

Dr. Wilson’s talk highlighted the progress and challenges in gene therapy for Angelman Syndrome. He emphasized the importance of developing efficient methods for delivering therapeutic genes to the CNS and expressed optimism for the future of gene therapy in treating rare diseases.