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Global Dementia Legacy Event
Neil Buckholtz, Ph.D.Director, Division of Neuroscience
National Institute on Aging
June 18, 2014
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International Alzheimer’s Disease Research Portfolio (IADRP)
• Developed by NIA in collaboration with Alzheimer’s Association.
• Will enable funders of Alzheimer’s research to coordinate planning, leverage resources, avoid duplication, and identify new opportunities.
• Will give the public a full picture of the scale of ongoing research on AD both nationally and internationally.
http://iadrp.nia.nih.gov/cadro-web/
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CADRO is a three-tier classification system created by NIA and the Alzheimer’s Association to capture the complete range of AD research
First level of classification consists of seven categories: 5 research and 2 research resources-related:
Category A – Molecular Pathogenesis and Physiology of Alzheimer’s Disease Category B – Diagnosis, Assessment and Disease Monitoring Category C – Translational Research and Clinical Interventions Category D – Epidemiology Category E – Care, Support and Health Economics of Alzheimer’s Disease Category F – Resources for the Research Community Category G – Consortia and Public Private Partnerships
Each category is divided into “research topics”; many topics further divided into “research themes”
Detailed classification will enable funders and researchers to identify research gaps, areas of overlap/duplication of effort, and opportunities for collaboration with much greater specificity
http://www.nia.nih.gov/research/dn/international-alzheimers-disease-research-portfolio
Common Alzheimer’s Disease Research Ontology (CADRO) Structure
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Web-based portal developed by NIA and the Alzheimer’s Association: Alzheimer’s and related dementias research funded projects 2008 to 2012.
Currently includes: Federal agencies (including NIH, AHRQ, CDC, AoA, VA and DoD), Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, and Alzheimer’s Research UK, Alzheimer’s Society UK, Alzheimer’s Society of Canada, and Alzheimer’s Australia.
Summer 2014: Additional funders (10) and 2013 data will be available on IADRP.
http://iadrp.nia.nih.gov/cadro-web/
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1. Amyloid32%
2. Tau6%
3. Presenilins4%
4. ApoE and Lipids9%
5. Brain Circuits and Synapses7%
6. Neurogenesis Cell Death
5%
7. Immunity and In-flammation
10%
8. Bioenergetics1%
9. Vascular/Metabolic Factors
5%
10. Hormones3%
11. Genetics11%
12. Other Pathogenic Mechanisms7%
Proportion of ‘Category A’ Projects by Topic across All Funding Organizations (2012)
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2008 2009 2010 2011 201220%
30%
40%
50%
60%
70%
80%
90%
100%
12. Other Pathogenic Mechanisms
11. Genetics
10. Hormones
9. Vascular/Metabolic Factors
8. Bioenergetics
7. Immunity and Inflammation
6. Neurogenesis Cell Death
5. Brain Circuits and Synapses
4. ApoE and Lipids
3. Presenilins
2. Tau
1. Amyloid
Changes in the Proportion of ‘Category A’ Projects by Topic for All Funding Organizations (2008 - 2012)
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Step 1 Funding organizations identify
their respective AD and AD-related dementia projects
Step 2 Funding organizations provide the IADRP Team with projects in a designated excel template or via links to projects online
along with specified data elements and abstracts
Step 3The IADRP Team codes
projects (via an automated coding portal) using the
Common Alzheimer's Disease Research Ontology (CADRO)
(http://www.nia.nih.gov/research/dn/cadro-outline)
Step 4Funding organizations validate
the coding via the coding portal
Step 5Coded and validated projects are uploaded into the IADRP
online database (http://iadrp.nia.nih.gov)
Portfolio AnalysisAll users can systematically
compare and analyze funding, composition of research,
specific trends in funding over time, geographic distribution of projects, and overlapping
funding priorities
IADRP Submission Process
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Accelerating Medicines Partnership
Alzheimer's Disease Program
8
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Why AMP? Why now?
Developing effective new medicines takes too long, costs too much and fails too often.
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AMP Pilots:Alzheimer’s disease
Type 2 diabetesRheumatoid arthritis/systemic lupus
erythematosus
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NIA Supported Secondary Prevention TrialsIdentify biomarkers correlated with therapeutic benefit in pre-symptomatic trials
Proposal Description Principal investigator
Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Trial
• Phase II/III study to assess the safety, tolerability, and biomarker efficacy of gantenerumab and solanezumab in mutation carriers
• Randall J. Bateman, WUSL• Collaborating companies:
– Lilly– Roche– Alzheimer's Assoc.– Avid Radiopharm.– Cog State
The Alzheimer's Prevention Initiative APOE4 Trial
• Testing an anti-amyloid drug (TBD) in cognitively normal older volunteers who are at increased risk of developing late-onset Alzheimer’s (APOE-e4 homozygotes)
• Eric Reiman, BANNER• Pierre Tariot, BANNER
Alzheimer’s Disease Cooperative Study Anti-
Amyloid Treatment in Asymptomatic AD Trial (A4)
• Secondary prevention trial of solanezumab in clinically normal older people with biomarker evidence of brain amyloid.
• Reisa Sperling, Harvard• Paul Aisen, UCSD
© The Boston Consulting Group, Inc.
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AMP Project A
• Supplement the imaging and fluid biomarker panels already included in these three NIH-funded Phase II/III registration trials in presymptomatic Alzheimer’s through the addition of tau PET imaging, EEG measures, and novel fluid biomarkers.
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Amyloid and Tau PET imaging
K. Johnson HAI 2014
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AMP Project B
• Apply integrated network analyses (RNA, proteomic, other “omic” studies) in 2500 human AD brain samples to identify biologic nodes and networks that are linked to the development or progression of AD to identify new targets for drug development.
• Create standardized open-source data structures and formats to aid the accessibility and ease of analysis of biological data in a manner not currently practiced in the AD field.
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Pathway discovery, validation and compound identification for Alzheimer's disease*Phil De Jager (Contact PI) Broad InstituteDavid Bennett Rush University
Integrative Biology Approach to Complexity of Alzheimer's Disease*Eric Schadt (Contact PI) Icahn Institute for Multiscale Biology at Mount Sinai & Dept of Genetics and Genomics Sciences
A System Approach to Targeting Innate Immunity in AD*Todd Golde (Contact PI) – University of FloridaNathan Price – Institute for Systems Biology, Seattle Nulifer Ertiken-Taner and Steven Younkin – Mayo Clinic Jacksonville
Funded Projects
Allan Levey (Contact PI) Emory University Discovery of Novel Proteomic Targets for Treatment of Alzheimer's Disease*
Lara Mangravite and Stephen Friend –Sage BionetworksAdministrative Supplements for Data Enablement and Data Integration
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Projected AMP funding contributions
Disease areaTotal project funding ($M)
Total NIH funding ($M)
Total industry
funding ($M)
AD 135 67.6 67.4
T2D 58.4 30.4 28.0
RA/SLE 41.6 20.9 20.7
Total 235 118.9 116.1
Industry is also providing AMP with additional in-kind contributions, e.g., clinical trials, drug, tracer, databases, etc.
© The Boston Consulting Group, Inc.
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AMP Participation by Disease AreaAlzheimer's
diseaseAlzheimer's
disease Type 2 DiabetesType 2 Diabetes RA, SLE & relatedRA, SLE & related
Industry members
Government members
Non-profit members
© The Boston Consulting Group, Inc.