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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
8:30 a.m. |
Welcome and Overview of Workshop
FRANCES JENSEN, Perelman School of Medicine, University of Pennsylvania (Chair) |
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.
8:45 a.m. |
Session Overview
SARAH CADDICK, Thalamic (Moderator) |
8:55 a.m. |
Speakers
GUOPING FENG, Massachusetts Institute of Technology HIDEYUKI OKANO, Keio University School of Medicine; RIKEN Brain Science Institute YOLAND SMITH, Yerkes National Primate Research Center; Emory University ANGELA ROBERTS, University of Cambridge |
9:55 a.m. | Discussion Discussant: WILLIAM NEWSOME, Stanford University |
10:30 a.m. | BREAK |
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).
10:45 a.m. |
Session Overview
ROBERT WURTZ, National Eye Institute (Scientist Emeritus) (Moderator) |
11:00 a.m. |
Speakers
MU-MING POO, Chinese Academy of Sciences BEN DEVERMAN, Broad Institute of Massachusetts Institute of Technology and Harvard University JEAN BENNETT, University of Pennsylvania KAREN PARKER, Stanford University |
12:00 p.m. |
Discussion
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Discussants: DAVID AMARAL, University of California, Davis ROBERT DESIMONE, Massachusetts Institute of Technology |
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12:30 p.m. | LUNCH |
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.
1:30 p.m. |
Session Overview
HENRY T. GREELY, Stanford University (Moderator) |
1:40 p.m. |
Speakers
MARGARET LANDI, GlaxoSmithKline STEFAN TREUE, German Primate Center; Georg-August University JEFFREY KAHN, Johns Hopkins University |
2:25 p.m. |
Discussion
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3:00 p.m. | BREAK |
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.
3:15 p.m. |
Session Overview
FRANCES JENSEN, Perelman School of Medicine, University of Pennsylvania (Chair) |
3:25 p.m. |
Keynote
MU-MING POO, Chinese Academy of Sciences |
3:40 p.m. |
Panel Discussion
JOHN MORRISON, California National Primate Research Center, University of California, Davis HIDEYUKI OKANO, Keio University School of Medicine; RIKEN Brain Science Institute JOSHUA GORDON, National Institute of Mental Health MARK FRASIER, The Michael J. Fox Foundation for Parkinson’s Research |
JOHN SPIRO, Simons Foundation Autism Research Initiative LISA STANEK, Sanofi |
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4:25 p.m. | Discussion |
5:15 p.m. |
Closing Remarks
STEVEN HYMAN, Broad Institute of Massachusetts Institute of Technology and Harvard University |
5:30 p.m. | Adjourn Workshop |
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