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Workshop Agenda

Transgenic and Chimeric Neuroscience Research: Exploring the Scientific Opportunities Afforded by New Nonhuman Primate Models—A Workshop

October 4, 2018
Keck Center of the National Academies
500 Fifth Street, NW, Washington, DC

Background:

The translational disconnect from preclinical studies with predominantly rodent animal models to human clinical trials remains a key challenge associated with lagging development of therapies for brain disorders. Since 2012, the Forum on Neuroscience and Nervous System Disorders has hosted a series of workshops examining different aspects of this challenge, including maximizing the translation of effective therapies from animal models to clinical practice and exploring the evidence needed to bring compounds that appear to be safe into human efficacy trials. While no animal model will fully recapitulate human nervous system disorders, nonhuman primates (NHPs)—such as marmosets and macaques—have shown promise in their ability to serve as models for complex brain disorders, given the phylogenetic proximity and genetic similarity to humans, similarity of neuroanatomical organization (e.g., a well-developed prefrontal cortex) and associated cognitive and behavioral functions, social cognition, and the ability to study developmental phenotypes and prodromal disease states.

Workshop Objectives:

This 1-day public workshop will bring together experts and key stakeholders from academia, government, industry, and nonprofit organizations to examine the scientific opportunities and challenges, as well as bioethical considerations, of genetically engineered nonhuman primate models for neuroscience research.

Invited presentations and discussions will be designed to:

• Discuss the state of the science of transgenic and chimeric neuroscience research and emerging models for nervous system disorders, and explore the potential usefulness of such models to enhance understanding of behavior and higher cortical function and advance therapeutic development.
• Examine current tools and technologies used in rodent models (e.g., transgenesis, chimera, adeno-associated viruses [AAVs], gene therapy, etc.) and explore how they would need to be modified for use in other animal models, such as nonhuman primates.
• Consider bioethical principles and issues related to genetic engineering of animal models for nervous system disorders, and discuss potential metrics for determining the models’ readiness for nonhuman primate research.
• Discuss policies and infrastructure needed to advance research in this domain including, for example, training, recruitment of early career scientists, and the potential development of specialized research centers and international collaborations.

DAY ONE: October 4, 2018

Session I: Emerging Transgenic and Chimeric Nonhuman Primate Models for Neuroscience Research and Therapeutic Development for Nervous System Disorders

Objective:

• Discuss the state of the science of transgenic and chimeric nonhuman primate models for nervous system disorders and explore the potential usefulness of such models to enhance understanding of behavior and higher cortical function and in translational science to advance therapeutic development.

Session II: Technology, Research Methodology, and Assessment Tools for Transgenic and Chimeric Nonhuman Primate Models

Objectives:

• Examine how current tools and technologies developed in rodent models (e.g., transgenesis, chimera, AAVs, gene therapy, in vitro fertilization, etc.) through the BRAIN Initiative and elsewhere might be modified for use in nonhuman primates.
• Consider potential logistical and feasibility issues unique to nonhuman primate models (e.g., cost).

Session III: Bioethical Considerations for Transgenic and Chimeric Nonhuman Primate Models in Neuroscience Research

Objectives:

• Explore bioethical principles and issues related to the genetic engineering of nonhuman primate models or the creation of chimeric nonhuman primate models for neuroscience research.
• Consider key questions that will necessitate nonhuman primate models for basic and translational research.
• Discuss potential safeguards needed for transgenic and chimeric nonhuman primate models of nervous system disorders to ensure proper animal welfare.

Session IV: Moving Forward: Policy and Infrastructure Needs to Advance Research

Objectives:

• Synthesize and discuss key highlights from the workshop presentations and discussions, including identifying next steps and promising areas for future action and research.
• Discuss policies and infrastructure needed to advance research in this domain, including, for example, training, recruitment of early career scientists, and the potential development of specialized research centers and international collaborations.
• Consider the roles of national primate research centers, governments, private philanthropy, and other key stakeholders to advance this research.

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