2020 Update on Gene Therapy for CNS Diseases

Quick Overview

In this presentation from the 2020 FAST Science Summit, Jim Wilson from the University of Pennsylvania provides an update on gene therapy for central nervous system (CNS) diseases. He discusses the challenges of viral-mediated gene therapy and the need for improved delivery methods to the CNS. Wilson explains the process of translational research, from animal models to human studies, and highlights the importance of demonstrating safety and efficacy. He discusses different routes of administration, including intravenous and direct injection into the brain, and the limitations and potential of each approach. Wilson also discusses the progress made in clinical trials of AAV gene therapy, with a focus on storage diseases and neurodegeneration. He concludes by discussing the path to gene therapy for Angelman syndrome, highlighting the need for improved efficiency in gene transfer to the brain.

Introduction

In this talk, Jim Wilson, a researcher from the University of Pennsylvania, provides an update on the progress of gene therapy for central nervous system (CNS) diseases. He highlights the challenges faced in viral-mediated gene therapy and the importance of developing approaches for inherited neurologic disorders.

The Journey from Bench to Bedside

Wilson explains the process of translational research, which involves conducting experiments in animal models to demonstrate the efficacy and safety of gene therapy interventions. He emphasizes the need to scale the dose and evaluate potential side effects in larger animals before moving on to human studies.

Overcoming the Blood-Brain Barrier

The primary challenge in gene therapy for CNS diseases is delivering enough of the gene to the central nervous system. Wilson discusses the blood-brain barrier, which prevents the transport of gene delivery vehicles called vectors from the blood to the neurons and target cells in the brain. He explores various methods to improve delivery, including developing modified vectors that can cross the blood-brain barrier.

Optimizing Route of Administration

Wilson discusses different routes of administration for gene therapy, such as intravenous delivery, direct injection into the brain, and injection into the cerebral spinal fluid. He explains the advantages and limitations of each approach and highlights the importance of targeting specific areas of the brain or specific cell types affected by the disease.

Progress in Clinical Trials

Wilson provides an overview of the current status of clinical trials for AAV gene therapy in humans. He mentions the number of ongoing trials and the focus on storage diseases, neurodegeneration, and emerging neurodevelopmental diseases. He also discusses the most common routes of administration and the use of AAV9 as the primary vector.

Challenges and Future Directions for Angelman Syndrome

Wilson shares his lab’s work on gene therapy for Angelman syndrome (AS), a neurodevelopmental disorder. He discusses the challenges of achieving efficient gene transfer in the brain and the need for further research to improve distribution. He presents promising results in mouse models and preliminary data from monkey studies, highlighting the importance of safety and efficacy in translating gene therapy to humans.

Conclusion

Wilson concludes by emphasizing the ongoing efforts to improve the efficiency of gene transfer in the brain for CNS diseases. He expresses optimism about the progress made so far and the potential for future advancements in gene therapy. He thanks the organizers of the 2020 FAST Summit and Gala for the opportunity to share this update with families and stakeholders interested in AS research.