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Workshop Agenda

Enabling Novel Treatments for Nervous System Disorders by Improving Methods for Traversing the Blood–Brain Barrier: A Workshop

September 8, 2017
Keck Center of the National Academies
500 Fifth Street, NW | Washington, DC

Background:

The blood–brain barrier (BBB) presents a special challenge to the development of therapeutics for many central nervous system (CNS) disorders. Far from acting simply as a physical barrier, the BBB is a complex dynamic system involving several cell types, passive and active transport mechanisms, and adaptive function to control the exchange of substances between the blood and the CNS. Few therapeutic agents readily traverse the BBB to reach the brain or spinal cord, including most small-molecule drugs and the vast majority of large molecules, such as proteins. Several research groups are exploiting intrinsic BBB transport mechanisms, such as molecular Trojan horses, and exploring technologies, such as chemical modifications and physical disruption, to test delivery of therapeutic agents to the CNS. Such strategies may greatly increase the armamentarium of potential drugs for treating psychiatric and neurological disorders. This public workshop will bring together key experts from academia, government, the biotechnology and pharmaceutical sector, disease-focused organizations, and other interested stakeholders to explore current development of novel methods for traversing the

BBB to deliver therapeutics for nervous system disorders and to identify potential opportunities for moving the field forward.

Workshop Objectives:

• Provide an overview of current knowledge on the role of the BBB biology and delivery mechanisms examining gaps in our current knowledge that future research may address.
• Discuss BBB passive and active mechanisms that challenge development and delivery of effective therapeutic interventions to CNS targets.
• Highlight current data and innovative approaches for delivery of therapeutics across the BBB harnessing methods, including chemical modifications, Trojan horse approaches, physical targeting and disruption, nanoparticles, ultrasound, and other technologies.
• Explore potential opportunities for catalyzing development of novel treatments that cross the BBB—from the preclinical to the clinical phase—with an emphasis on risks, levers, and potential collaborative efforts among sectors.

September 8, 2017, Room 100

Session Objectives:

• Provide background information about BBB biology, including its function in health and disease states and active and passive mechanisms challenging delivery of therapeutics to the CNS.
• Review different mechanisms and modes for traversing the BBB for the purpose of therapeutic delivery to the CNS.
• Highlight gaps in our understanding of BBB biology and transport mechanisms for delivery of therapeutics to the brain.

Session Objectives:

• Describe current understanding of modalities for traversing the BBB.
• Survey innovative technologies—including Trojan horse approaches, physical targeting and disruption, nanoparticles, and ultrasound—for delivery of therapeutics to the CNS.
• Discuss desirable characteristics for development of new technologies for traversing the BBB.

Session Objectives:

• Discuss the translation—from late preclinical work to clinical trials—of delivery strategies for traversing the BBB, including delivery of synthetic molecules, biologics, and gene therapy.
• Describe the limitations of current methods for traversing the BBB and identify research and other potential next steps that would move the field forward.

Session Objectives:

• Discuss approaches, tools, and lessons learned from other regulatory domains that may advance the development and translation of novel methods to traverse the BBB.
• Identify specific barriers and opportunities in the regulatory domain related to the development and application of methods for traversing the BBB.
• Explore issues related to critical attributes and potency assays; safety, including immunogenicity and CNS toxicity; and animal models, including appropriate species selection.
• Explore best practices and strategies to facilitate regulatory consideration of novel technologies for traversing the BBB.

Session Objectives:

• Identify specific barriers and opportunities for increased coordinating among ongoing efforts in academia, the private sector, and federal agencies.
• Brainstorm potential collaborative projects that could be submitted through current or planned mechanisms.
• Explore novel mechanisms for catalyzing innovative technologies for traversing the BBB through new public–private partnerships and consortia, including discussion of potential practical next steps.