Neurodegeneration: Opportunities for Collaboration Across Disease-Specific Research and Development Communities—A Workshop
April 30-May 1, 2012
Pew DC Conference Center 901 E Street, NW, Washington, DC
Background: Neurodegenerative diseases are becoming increasingly prevalent in the United States due to the aging population. Implications of these diseases are grave, both for individual and family quality of life and for health care costs. Recent findings have revealed potential commonalities and parallelisms in genetic and cellular mechanisms across neurodegenerative diseases. Enhanced sharing of research findings and collaboration across research communities could potentially help advance basic scientific knowledge about each disease and about neurodegeneration and neurodegenerative diseases in general. Furthermore, enhanced basic scientific understanding could facilitate therapeutics development for neurodegenerative disorders, including therapeutics that may address more than one neurodegenerative disease. This workshop will explore commonalities across neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia, and identify potential opportunities for collaboration across the respective research and development communities. Speakers and participants will be invited from academia; pharmaceutical and biotechnology industries; government agencies such as the National Institutes of Health, the National Science Foundation, and the Department of Veterans Affairs; and disease advocacy groups.
Meeting Objectives: The objectives of this workshop are to look across the neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, ALS, and frontotemporal dementia—and
• Identify and discuss commonalities related to genetic and cellular mechanisms.
• Identify areas of fundamental science needed to facilitate therapeutics development.
• Explore areas of potential collaboration among the respective research communities and sponsors.
DAY ONE: April 30, 2012
8:00 a.m. |
Welcome and Opening Remarks
STORY LANDIS, Workshop Co-Chair Director National Institute of Neurological Disorders and Stroke |
JOHN TROJANOWSKI, Workshop Co-Chair Co-director, Center for Neurodegenerative Disease Research University of Pennsylvania |
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8:10 a.m. |
U.S. Department of Veterans Affairs and Neurodegeneration Research: Current Efforts and Future Goals
JOEL KUPERSMITH Chief Research and Development Officer U.S. Department of Veterans Affairs |
SESSION 1: OVERVIEW OF COMMON FEATURES ACROSS NEURODEGENERATIVE DISEASES
Session Objectives: The objectives of this session are to provide a genetic, clinical, and pathological framework to the notion that commonalities exist across neurodegenerative diseases. While this meeting focuses on discrete diagnostic entities, it is likely that this section may use examples from entities that cross these boundaries. Specifically, this session will
• Provide an overview of the genetic complexity of different neurodegenerative diseases.
• Discuss common and distinguishing features of the genetics of different neurodegenerative diseases.
• Discuss the clinical heterogeneity of monogenic disorders.
• Describe and discuss how pathology is likely to inform us about etiologic overlap between entities and provide illustrative examples of this overlap.
• Discuss the rationale for looking across neurodegenerative diseases to advance scientific understanding and explore innovative approaches to therapeutics development.
8:20 a.m. |
Genetic Overlap and Complexity of Phenotypical Expression
ANDREW SINGLETON, Session Chair Senior Investigator, Laboratory of Neurogenetics National Institute on Aging |
8:30 a.m. |
Pathological Overlap
DENNIS W. DICKSON Professor of Laboratory Medicine and Pathology Mayo Clinic |
8:40 a.m. |
Translational Route Challenges: Is Combining Diseases Informative or a Distraction?
ADRIAN J. IVINSON Director, Harvard NeuroDiscovery Center Harvard Medical School |
8:50 a.m. | Discussion Among Speakers and Attendees |
SESSION 2: PROTEIN AGGREGATION IN NEURODEGENERATIVE DISEASES
Session Objectives: The objectives of this session are to look at protein aggregation across the neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, and frontotemporal dementia—and
• Highlight commonalities related to protein aggregation across these diseases, for example, autophagy.
• Discuss promising opportunities for collaboration among the respective research communities.
• Identify areas of fundamental research about protein aggregation that would facilitate biomarker and therapeutics development.
• Identify the next steps that research sponsors, investigators, and others should take to facilitate collaborative research and drug development in this area, including frameworks for partnerships and collaboration.
9:10 a.m. |
Overview of Status of the Field and Session Objectives
JOHN DUNLOP, Session Co-Chair Vice President, Discovery Neuroscience Innovative Medicine Unit AstraZeneca |
LUCIE BRUIJN, Session Co-Chair Chief Scientist ALS Association |
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9:20 a.m. |
Proteostasis Challenges in Neurodegenerative Diseases
RICK MORIMOTO Professor of Molecular Biosciences Northwestern University |
9:30 a.m. | Discussion Among Speakers and Attendees |
9:45 a.m. |
The Selective Degradation of Misfolded Proteins and Protection Against Neurodegenerative Diseases
ALFRED GOLDBERG Professor of Cell Biology Harvard Medical School |
9:55 a.m. | Discussion |
10:10 a.m. | BREAK |
10:25 a.m. |
Autophagy in Neurodegenerative Disease
ANA MARIA CUERVO Professor, Department of Developmental and Molecular Biology Albert Einstein College of Medicine |
10:35 a.m. | Discussion |
10:50 a.m. |
Protein Aggregation in ALS and Huntington’s Disease
CLAUDIO HETZ Professor, University of Chile Adjunct Professor, Harvard School of Public Health |
11:00 a.m. | Discussion |
11:15 a.m. |
Development of Assay Systems in Observing Aggregates and Development of Small Molecules
STEVEN FINKBEINER Director, Taube-Koret Center, Gladstone Institute for Neurodegenerative Disease Professor, University of California, San Francisco |
11:25 a.m. | Discussion |
11:40 a.m. |
Drug Discovery Efforts
WARREN HIRST Associate Research Fellow, Neurodegeneration & Neurologic Diseases Pfizer |
11:50 a.m. | Discussion |
12:30 p.m. | LUNCH |
SESSION 3: MITOCHONDRIAL PATHOLOGY AND NEURODEGENERATIVE DISEASE
Session Objectives: The objectives of this session are to look at mitochondrial pathobiology across the neurodegenerative diseases—including Alzheimer’s disease and other dementias, Parkinson’s disease, and ALS—and to
• Highlight differences and commonalities related to mitochondrial dysfunction and pathology across the diseases.
• Discuss opportunities for the development of mitochondriarelated biomarkers and therapeutic interventions.
• Identify next steps that research sponsors, investigators, and others should take to facilitate collaborative research and drug development in this area, including frameworks for partnerships and collaboration.
1:30 p.m. |
Overview of Status of the Field and Session Objectives
LENNART MUCKE, Session Chair Director and Senior Investigator, Gladstone Institute of Neurological Disease Professor of Neurology and Neuroscience University of California, San Francisco |
1:40 p.m. |
Systems Biology and Disease
VAMSI K. MOOTHA Professor Department of Systems Biology, Harvard Medical School Department of Medicine, Massachusetts General Hospital |
1:50 p.m. | Discussion Among Speakers and Attendees |
2:05 p.m. |
Neuronal Cell Death in Human Neurological Disorders and Their Animal/Cell Models
LEE MARTIN Professor of Pathology, Neuroscience Johns Hopkins University |
2:15 p.m. | Discussion |
2:30 p.m. |
Parkinson’s Disease
RICHARD J. YOULE Senior Investigator National Institute of Neurological Disorders and Stroke |
2:40 p.m. | Discussion |
2:55 p.m. | BREAK |
3:10 p.m. |
ALS and Huntington’s Disease
NEIL KOWALL Professor of Neurology and Pathology, Boston University Chief of Neurology, VA Boston Healthcare System |
3:20 p.m. | Discussion |
3:35 p.m. |
Alzheimer’s Disease
DOUGLAS C. WALLACE Director, Center for Mitochondrial and Epigenomic Medicine Michael and Charles Barnett Chair of Pediatric Mitochondrial Medicine and Metabolic Disease The Children’s Hospital of Philadelphia |
3:45 p.m. | Discussion |
4:45 p.m. |
Wrap-Up: Highlights and Key Themes of Day One
STORY LANDIS, Workshop Co-Chair JOHN TROJANOWSKI, Workshop Co-Chair |
5:00 p.m. | ADJOURN DAY ONE |
DAY TWO: May 1, 2012
8:00 a.m. |
Welcome and Objectives of Day Two
STORY LANDIS, Workshop Co-Chair Director National Institute of Neurological Disorders and Stroke |
JOHN TROJANOWSKI, Workshop Co-Chair Co-director, Center for Neurodegenerative Disease Research University of Pennsylvania |
SESSION 4: NEURODEGENERATIVE DISEASE TRANSMISSION AND IMMUNE THERAPY
Session Objectives: The objectives of this session are to
• Provide an overview of the latest concepts on transmission of neurodegenerative diseases, including evidence that suggests that disease progression may occur through the cell-to-cell spread of pathological disease proteins.
• Explore how targeting transmissible species of α -Synuclein as well as tau and Abeta using immune therapy may be used to treat Parkinson’s disease and Alzheimer’s disease, respectively.
• Identify the next steps that research sponsors, investigators, and others should take to facilitate collaborative research and drug development in this area, including frameworks for partnerships and collaboration.
8:15 a.m. |
Overview of Status of the Field and Session Objectives
JOHN TROJANOWKSI, Session Chair Co-director, Center for Neurodegenerative Disease Research University of Pennsylvania |
8:25 a.m. |
Transmission of Prions and Alzheimer’s Disease Abeta Amyloid
CLAUDIO SOTO Professor of Neurology Director, Center for Alzheimer’s Disease and Related Brain Disorders The University of Texas Medical School at Houston |
8:35 a.m. | Discussion Among Speakers and Attendees |
8:50 a.m. |
Transmission of Alzheimer’s Disease Abeta Amyloid
LARY C. WALKER Research Professor of Neuroscience Emory University |
9:00 a.m. | Discussion |
9:15 a.m. |
Transmission of Alzheimer’s Disease Tau Amyloid
KAREN DUFF Professor, Department of Pathology Columbia University |
9:25 a.m. | Discussion |
9:40 a.m. | BREAK |
10:00 a.m. |
Transmission of Parkinson’s Disease α-Synuclein Amyloid
VIRGINIA M.-Y. LEE The John H. Ware 3rd Professor in Alzheimer’s Research Department of Pathology and Laboratory Medicine Director, Center for Neurodegenerative Disease Research University of Pennsylvania School of Medicine |
10:10 a.m. | Discussion |
10:25 a.m. |
α-Synuclein Immunization for Parkinson’s Disease
DORA GAMES Head of Pharmacology Neotope Biosciences |
10:35 a.m. | Discussion |
10:50 a.m. |
Tau Immunization for Alzheimer’s Disease and Related Tauopathies
PETER DAVIES Head Litwin-Zucker Center for the Study of Alzheimer’s Disease and Memory Disorders The Feinstein Institute for Medical Research |
11:00 a.m. | Discussion |
11:45 a.m. | LUNCH |
SESSION 5: ERRORS IN RNA
Session Objectives: The objectives of this session are to
• Discuss how errors in RNA-binding proteins are causes of neurodegenerative diseases, including ALS, frontotemporal dementia, and spinal muscular atrophy, as well as triplet nucleotide expansion as a risk factor in disease (e.g., ataxin and ALS).
• Discuss disease mechanisms for diseases with toxic RNAs, including myotonic dystrophy and other triplet nucleotide repeats where there are toxic RNAs or aberrant translation of the expansions.
• Explore potential biomarkers and therapies for RNA-binding protein errors in SMA, TDP-43, FUS, and C9orf72.
• Discuss yeast models to identify therapeutics and the emerging roles of non-coding RNA networks in the pathogenesis of neurodegenerative diseases.
• Identify the next steps that research sponsors, investigators, and others should take to facilitate collaborative research and drug development in this area, including frameworks for partnerships and collaboration.
12:45 p.m. |
Overview of Status of the Field and Session Objectives
DON CLEVELAND, Session Chair Professor and Chair, Department of Cellular and Molecular Medicine Head, Laboratory for Cell Biology Ludwig Institute for Cancer Research University of California, San Diego |
12:55 p.m. |
Overview of RNA Gain-of-Function Mechanisms in Neurodegenerative Disease
LAURA RANUM Professor of Molecular Genetics and Microbiology University of Florida |
1:05 p.m. | Discussion |
1:20 p.m. |
Overview of Therapies for RNA-Binding Protein Errors
FRANK RIGO Assistant Director, Core Antisense Research ISIS Pharmaceuticals, Inc. |
1:30 p.m. | Discussion |
1:45 p.m. |
Yeast Models to Identify Therapeutics
GREGORY A. PETSKO Gyula and Katica Tauber Professor of Biochemistry & Chemistry Brandeis University |
1:55 p.m. | Discussion |
2:10 p.m. |
The Emerging Roles of Non-Coding RNA Networks in the Pathogenesis of Neurodegenerative Diseases
MARK F. MEHLER Alpern Professor of Neurology, Neuroscience and Psychiatry and Behavioral Sciences University Chair, The Saul R. Korey Department of Neurology Albert Einstein College of Medicine |
2:20 p.m. | Discussion |
2:45 p.m. | BREAK |
SESSION 6: FUTURE DIRECTIONS AND NEXT STEPS
Session Objectives: A panel will synthesize and discuss key highlights from the workshop presentations and discussions, including
• Identify key promising areas for future cross-disease research and collaboration.
• Discuss opportunities for partnerships—public–private and across disease-specific communities—to advance neurodegeneration research and therapeutics development.
• Discuss challenges to advancing research and therapeutics development for the neurodegenerative diseases and potential mechanisms to address these challenges.
3:00 p.m. |
Panel Discussion (Session Chairs from Previous Sessions):
STORY LANDIS, Session Co-Chair Director National Institute of Neurological Disorders and Stroke |
JOHN TROJANOWSKI, Session Co-Chair Co-director, Center for Neurodegenerative Disease Research University of Pennsylvania |
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ANDREW SINGLETON Senior Investigator, Laboratory of Neurogenetics National Institute on Aging |
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JOHN DUNLOP Vice President, Discovery Neuroscience Innovative Medicine Unit AstraZeneca |
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LUCIE BRUIJN Chief Scientist ALS Association |
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LENNART MUCKE Director and Senior Investigator, Gladstone Institute of Neurological Disease Professor of Neurology and Neuroscience University of California, San Francisco |
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DON CLEVELAND Professor and Chair, Department of Cellular and Molecular Medicine Head, Laboratory for Cell Biology Ludwig Institute for Cancer Research University of California, San Diego |
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3:30 p.m. | Discussion Among Speakers and Attendees |
4:30 p.m. | ADJOURN |