Advisory Council December 2013 Meeting Presentation: Research Progress Report

ADVISORY COUNCIL ON ALZHEIMER'S RESEARCH, CARE, AND SERVICES

Monday, December 2, 2013

NAPA Research Progress Report

Richard J. Hodes, M.D.
Chair, Federal Research Subcommittee

Predicted Mechanisms of LOAD GWAS Alzheimer’s Disease Associated Genes

Innate immune/ brain inflammatory response	Endocytosis and cellular protein trafficking including APP trafficking	Lipid transport/ metabolism	Synaptic transmission	Cytoskeletal function
HLA-DRB5/HLA-DRB1 TREM2 CR1 CLU MS4A4/MS4A6E EPHA1 INPP5D ABCA7	SORL1 PICALM BIN1 CD2AP	APOE CLU ABCA7	PTK2B MEF2C	CELF1 NME8 CASS4 FERMT2
Nature Genetics (Oct. 27, 2013)

Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease

2013 RFA: Interdisciplinary Approach to Identification and Validation of Novel Therapeutic Targets for AD

Supports interdisciplinary and integrative research focused on identification and preclinical validation of novel targets for AD treatment and prevention
- Encourages the pursuit of paradigm-shifting biological and therapeutic hypotheses and promotes the creation of new translational teams
- Encourages the use of network-based approaches, such as systems biology and systems pharmacology to gain understanding of the molecular and physiological context within which potential therapeutic targets operate
U01-A Systems Approach to Targeting Innate Immunity in Alzheimer’s -- Dr. Todd Golde, University of Florida, and Colleagues
U01-Pathway Discovery, Validation and Compound Identification for Alzheimer’s Disease -- Drs. Philip De Jager, Brigham and Women's Hospital, Broad Institute, Harvard University, Boston, and David Bennett, Rush University Medical School, Chicago
U01-Integrative Biology Approach to Complexity of Alzheimer’s Disease -- Dr. Eric Schadt of Icahn School of Medicine at Mount Sinai, New York City, and Team of investigators

Identification and Validation of Novel Therapeutic Targets for Alzheimer's Disease, RFA-AG-13-013: http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-13-013.html

2013 RFA: Alzheimer's Disease Prevention Trials

Phase II or Phase III clinical trials testing pharmacological (small molecules and biologics) and non-pharmacological interventions, in cognitively normal individuals at-risk for AD (e.g., individuals at risk genetically, older adults positive for biomarker evidence of Alzheimer’s disease pathology) or in individuals with MCI using a combination of biomarkers (fluid and imaging) and cognitive measures as outcomes.
UF1 - The Alzheimer's Prevention Initiative APOE4 Trial -- Drs. Eric Reiman and Pierre Tariot, Banner Alzheimer’s Institute, Phoenix, and Co-investigators
U01 -- Stimulating the Innate Immune System to Prevent Alzheimer’s -- Dr. Ted Ashburn, Sanofi Aventis, Cambridge, Mass., in partnership with Baylor College of Medicine, Houston, Texas

Not supported from RFA, but part of FY 2013 AD Funds:

U01 -The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Trial -- Dr. Randall Bateman, Washington University, St. Louis, MO, and Co-investigators

AD Prevention Trials, RFA-AG-13-015: http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-13-015.htm

2013 RFA: Alzheimer's Disease Phase I Clinical Trials

Provide support for first-in-human studies for promising AD therapeutics.
Evaluate the metabolic and pharmacological actions of drugs, including biologics in humans.
UF1- Allopregnanolone Regenerative Therapeutic for MCI/Alzheimer’s: Dose Finding Phase 1 -- Drs. Roberta Brinton and Lon Schneider, University of Southern California, Los Angeles

AD Phase I Clinical Trials , RFA-AG-13-016: http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-13-016.htm

Alzheimer's Disease-Related Dementias: Research Challenges and Opportunities

Sponsored by the National Institute of Neurological Disorders and Stroke in cooperation with:

National Institute on Aging
Alliance for Aging Research, ACT-AD
Alzheimer's Association
Association for Frontotemporal Degeneration
USAgainst Alzheimer's

http://www.ninds.nih.gov/ADRelatedDementias2013

CONFERENCE

Goals
- Each topic area presents rationale for prioritized research recommendations and timelines
- Provoke discussion among group experts
- Solicit feedback and opinions from audience
Outcomes
- 567 registrants: 322 in-person, > 200 on-line
- Lively 2-day public session with many comments
  - Culminated with “open mike” and review of all suggested revisions
- Closed session to plan post-conference work

EXECUTIVE SUMMARY - Overall

Topic Area	Focus Area (number of prioritized research recommendations)
1. Multiple etiology dementias (MED)	Differential Diagnosis (3)		Epidemiology (3)
2. Health disparities (HD)	Recruitment (4)		Advancing Treatment and Prevention Strategies (4)
3. Lewy body dementias (LBD)	1. Establish longitudinal cohorts with common measures, culminating in autopsy studies. (2)	2. Discover disease mechanisms through brain mapping and genetics (2)	3. Development and validate biological and imaging biomarkers (2)	4. Model disease processes to develop potential symptomatic and disease modifying therapies (2)
4. Frontotemporal dementia and other tauopathies (FTD)	Basic Science: Pathogenesis and Toxicity (4)		Clinical Science: Discovery, tools, and cohorts (4)
5. Vascular contributions to ADRD - focus on small vessel disease and AD/vascular interactions (VAS)	Basic Mechanisms and Experimental Models (3)		Human-Based Studies (3)

EXECUTIVE SUMMARY – Overlap

Although ordering of priorities and timelines differed, several recs applied across ADRD (and AD)
- Fundamental research to fill critical knowledge gaps
- Training and education to ensure durable progress
- Improved diagnostics
- Optimized repositories
- All recommendations within HD
- Culmination of research in effective interventions

Alzheimer's Disease Summit: The Path to 2025

November 6 - 7, 2013
The New York Academy of Sciences
Presented by The New York Academy of Sciences, National Institute on Aging/NIH and the Global CEO Initiative on Alzheimer's Disease

Primary Goal: To convene leading industry, academic, and government stakeholders in discussions regarding how to prevent and effectively treat Alzheimer's by 2025:
- Coordinating with governmental efforts to build research resources
- Reengineering our current drug development and evaluation systems
- Identifying innovative technologies and financing models
Outcome: To comprise a research agenda that will delineate the pathways needed to effectively treat and prevent Alzheimer's disease by 2025.

http://www.nyas.org/pathto2025