On April 23 and 24, 2019 the Forum on Neuroscience and Nervous System Disorders convened a workshop titled “Advancing Gene-Targeted Therapies for Central Nervous System Disorders” in Washington, DC. This public workshop brought together experts and key stakeholders from academia, government, industry, philanthropic foundations, and disease/patient-focused nonprofit organizations to explore approaches for advancing the development of gene-targeted therapies for central nervous system (CNS) disorders, and implications of developing these therapies. Participants explored lessons learned from both successful and unsuccessful clinical development programs; new knowledge about the genetic underpinnings of brain disorders; the current status and future potential of gene-targeted therapies for CNS disorders; challenges and potential solutions for translating preclinical findings to approved therapies; and patient and caregiver perspectives. They also discussed what will be needed to develop these therapies for common disorders such as Alzheimer's and Parkinson's disease, as well as neuropsychiatric and neurodevelopmental disorders such as schizophrenia and autism. The workshop included approaches that target both DNA and RNA, as well as gene products using viral vectors, antisense oligonucleotides, and RNA interference. This publication summarizes the presentations and discussion of the workshop.

Contents

• The National Academies of SCIENCES • ENGINEERING • MEDICINE
• PLANNING COMMITTEE ON ADVANCING GENE THERAPY FOR NERVOUS SYSTEM DISORDERS
• FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS
• Reviewers
• 1. Introduction and Overview
  • WORKSHOP OBJECTIVES
  • ORGANIZATION OF THE PROCEEDINGS
• 2. Exploring the Current Landscape of Central Nervous System Gene-Targeted Therapies
  • APPROVED GENE-TARGETED THERAPIES FOR MONOGENIC CENTRAL NERVOUS SYSTEM DISORDERS
  • UNSUCCESSFUL GENE THERAPY TRIALS: LESSONS LEARNED
• 3. Gene-Targeted Therapy Approaches for Central Nervous System Disorders: Opportunities and Challenges
  • DELIVERY OF GENE-TARGETED THERAPIES TO THE CENTRAL NERVOUS SYSTEM
  • IDENTIFYING THERAPEUTIC TARGETS
• 4. Translating Gene-Targeted Therapies from Bench to Bedside
  • ENABLING TRANSLATION WITH PRECLINICAL MODELS
  • CLINICAL TRIAL DESIGN CHALLENGES FOR GENE-TARGETED THERAPIES
  • REGULATORY PATHWAYS
  • MANUFACTURING CAPACITY
• 5. Meaningful Engagement of Patients and Families
  • FACILITATING PATIENT AND FAMILY ENGAGEMENT
  • ACCESS, COST, AND EQUITY
• 6. Future Directions in the Development of Gene-Targeted Therapies
  • NEW TECHNOLOGIES ON THE HORIZON
  • DIVERSE EXPERTISE NEEDED TO TACKLE DELIVERY CHALLENGES
  • MOVING BEYOND MONOGENIC DISORDERS
  • TARGETING NON-CODING RNAs
  • POTENTIAL FOR PRE-COMPETITIVE COLLABORATION
  • FINAL REMARKS
• Appendix A. References
• Appendix B. Workshop Agenda
• Appendix C. Registered Attendees

Suggested citation:

National Academies of Sciences, Engineering, and Medicine. 2019. Advancing gene-targeted therapies for central nervous system disorders: Proceedings of a workshop. Washington, DC: The National Academies Press. https://0-doi-org.brum.beds.ac.uk/10.17226/25529.

Digital Object Identifier: https://0-doi-org.brum.beds.ac.uk/10.17226/25529

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