Peer Reviewed Alzheimer s Research Program (PRARP)

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1 Peer Reviewed Alzheimer s Research Program (PRARP) Col Wanda L. Salzer, USAF Director, CDMRP Anthony Pacifico, Ph.D. Program Manager, PRARP

2 Disclaimer The information in this presentation is the opinion of the presenter. The briefing does not reflect Department of Defense (DoD) policy or opinion on Alzheimer s or traumatic brain injury (TBI) research. U.S. Army Medical Research and Materiel Command 2

3 Who is the CDMRP? Department of Defense Department of the Army Army Medical Command Medical Research and Materiel Command Congressionally Directed Medical Research Programs U.S. Army Medical Research and Materiel Command 3

CDMRP Factoids CDMRP manages extramural research programs directed by Congress Started in 1992 with Breast Cancer, now 27 programs Congress specifies disease area, CDMRP determines research strategy

4 CDMRP Factoids CDMRP manages extramural research programs directed by Congress Started in 1992 with Breast Cancer, now 27 programs Congress specifies disease area, CDMRP determines research strategy and competitively selects the best projects Unique public/private partnership encompassing the military, scientists, disease survivors, consumers, and policy makers Funds high-impact, innovative medical research to find cures, reduce the incidence of disease and injury, improve survival, and enhance the quality of life for those affected Nationally Focused: Alzheimer s Amyotrophic Lateral Sclerosis Autism Bone Marrow Failure Breast Cancer Duchenne Muscular Dystrophy Gulf War Illness Lung Cancer Multiple Sclerosis Neurofibromatosis NET Parkinson s Ovarian Cancer Peer Reviewed Cancer Peer Reviewed Medical Prostate Cancer Tuberous Sclerosis Complex Service Member Focused: Alcohol & Substance Abuse Disorders Defense Medical R & D Epilepsy Joint Warfighter Military Burn Orthotics & Prosthetics Peer Review Orthopaedic Psychological Health/ Traumatic Brain Injury Reconstructive Transplant Spinal Cord Injury Vision Research U.S. Army Medical Research and Materiel Command 4

Goal of the Two-Tier Review Process Mission: Responsibly manage collaborative research that discovers, develops, and delivers healthcare solutions for Service Members, Veterans, and the American

5 Goal of the Two-Tier Review Process Mission: Responsibly manage collaborative research that discovers, develops, and delivers healthcare solutions for Service Members, Veterans, and the American public. Peer Review Partnership Programmatic Review Criterion-based evaluation of full proposal Determination of absolute scientific merit Outcome: Written critique and scores for individual criteria and overall merit Comparison among proposals of high scientific merit Determination of adherence to intent and program relevance Outcome: Funding recommendations No standing peer review panels No contact between reviewers and applicants No pay line (portfolio balance) Funds obligated up front; no out-year budget commitments (but milestones imposed) No continuation funding U.S. Army Medical Research and Materiel Command 5

6 PRARP Vision and Mission Vision To address the long-term consequences of traumatic brain injury (TBI) as they pertain to Alzheimer's disease (AD). Mission The PRARP is devoted to 1) understanding the association between TBI and AD; and 2) reducing the burden on caregivers and affected individuals, especially in the military and Veteran community. U.S. Army Medical Research and Materiel Command 6

PRARP Factoids Stood up in 2011 $51 million FY11-FY14 $12 million FY15 29 awards FY11-FY13 13 awards recommended for funding FY14 Program Steering

7 PRARP Factoids Stood up in 2011 $51 million FY11-FY14 $12 million FY15 29 awards FY11-FY13 13 awards recommended for funding FY14 Program Steering Committee consists of governmental experts (NIH, DoD, and VA) Program supports datasharing (e.g., FITBIR) U.S. Army Medical Research and Materiel Command 7

8 FY11-FY13 AD Funding Breakdown PRARP Funding by CADRO Code PRARP-Funded Awards by CADRO Code Category C. Translational Research and Clinical Interventions, $360,417 (1%) Category D. Epidemiology, $1,440,893 (5%) Category E. Care, Support and Health Economics of Alzheimer s Disease, $1,676,086 (5%) Category A. Molecular Pathogenesis and Physiology of Alzheimer s Disease, $7,715,770 (24%) Category C. Translational Research and Clinical Interventions, 1 (4%) Category E. Care, Support and Health Economics of Alzheimer s Disease, 3 (10%) Category B. Diagnosis, Assessment and Disease Montoring, $20,890,055 (65%) Category D. Epidemiology, 4 (14%) Category B. Diagnosis, Assessment and Disease Montoring, 9 (31%) Category A. Molecular Pathogenesis and Physiology of Alzheimer s Disease, 12 (41%) CADRO = Common Alzheimer s Disease Research Ontology U.S. Army Medical Research and Materiel Command 8

9 Award Mechanisms Mechanism Eligibility Intent Funding Convergence Science Research Award (CSRA) Quality of Life Research Award (QUAL) Military Risk Factor Award (MRFA) Principal Investigators (PIs) at or above the level of Assistant Professor (or equivalent) from any field or discipline, who seek to bring their expertise to address the PRARP s mission; the research team must demonstrate TBI/AD experience. Supports research to generate resources and tools, or novel research efforts for researchers and/or practitioners in health sciences related to the PRARP s mission. Supports research to reduce the burden on caregivers and affected individuals, especially in the military and Veteran communities. The research impact will benefit the military, Veteran, and civilian communities. Facilitates high-impact, systematic, population-based research investigating the association between TBI and the subsequent development of AD. Maximum funding of $500,000 for direct costs (plus indirect costs) Maximum period of performance is 3 years Maximum funding of $5,000,000 for total costs Maximum period of performance is 5 years U.S. Army Medical Research and Materiel Command 9

10 FY14 Overarching Challenges # Overarching Challenge CSRA QUAL MRFA 1 Paucity of Research Resources: The paucity of research resources to examine the interrelationship between TBI and subsequent AD for military Veterans. 2 Paucity of Clinical Studies: The paucity of clinical or epidemiological studies to examine the interrelationship between TBI and subsequent AD for military Veterans. 3 Diagnostic Technologies, Tests, or Devices: The need for technologies, tests, or devices to detect the progression to AD subsequent to TBI. 4 Quality of Life: The need for technologies, assessments, interventions, or devices to benefit individuals living with the symptoms of TBI and AD. 5 Caregiver Burden: The need for technologies, assessments, interventions, or devices with the goal of reducing burden for caregivers of individuals living with the symptoms of TBI and AD. U.S. Army Medical Research and Materiel Command 10

11 FY14 Focus Areas # Focus Area CSRA QUAL MRFA 1 Genomics/Proteomics/Bioinformatics: Studies or technologies (e.g., genetic, proteomic and epigenetic strategies) intended to characterize neurological change(s) associated with TBI and subsequent AD. In addition, relevant technologies or tests may be considered under this focus area. 2 Pathology of Tau: Novel research and technologies dedicated to unraveling the basic pathological mechanisms of Tau associated with TBI and AD. 3 Roles of non-neuronal cells in TBI/AD pathogenesis: Technologies, tests, studies, or devices that will examine the roles of astrocytes (or other nonneuronal cells) in AD neurodegeneration due to TBI. 4 Care Interventions and Quality of Life: Research intended to stabilize or improve the quality of life of those affected by TBI or AD. Examples of research in this focus area include: identification and management of comorbidities and modifiable risk factors (e.g., sleep apnea, obesity), cognitive training interventions, studies of health and wellness and behavioral interventions. 5 Caregiver support: Research intended to reduce the burden of care on the caregiver for individuals affected by the symptoms of TBI or AD. Examples of research in this focus area include: caregiver training, home-based support, behavioral interventions, and relationship interventions. 6 Imaging: Development and application of anatomic and molecular imaging strategies to characterize neurological change associated with TBI and subsequent AD. 7 Novel Target Identification: Basic research (non-human) directly leading to the identification of new targets for the development of existing or new investigational medicines, drugs, or agents. U.S. Army Medical Research and Materiel Command 11

12 Discouraged Areas of Research The following is specifically discouraged under the FY15 PRARP: Pharmacologic Interventions: Clinical or Basic research requiring investigational or Food and Drug Administration-approved drugs or medicines. U.S. Army Medical Research and Materiel Command 12

Dr. Bruce Lamb Cleveland Clinic Novel Genetic Models to Study the Role of Inflammation in Brain Injury-Induced Alzheimer's Pathology

the brain. Using an injury model with mice that overproduce beta-amyloid, Dr.

Altered Immune Reaction in a Mouse Model of AD (R1.

13 Dr. Bruce Lamb Cleveland Clinic Novel Genetic Models to Study the Role of Inflammation in Brain Injury-Induced Alzheimer's Pathology Project tracks two different sources of inflammation; namely the peripheral monocytes of the bloodstream and the microglia innate to the brain. Using an injury model with mice that overproduce beta-amyloid, Dr. Lamb showed that beta-amyloid exacerbated the growth of the injury compared to controls. Altered Immune Reaction in a Mouse Model of AD (R1.40) Compared to Non- Transgenic Controls in Various Brain Regions Following TBI Model of How the Inflammatory Cascade Following TBI Impacts AD Pathologies Worsened Age-Related Cognition in a Mouse Model of AD (R1.40) Compared to Non-Transgenic Controls in Following TBI U.S. Army Medical Research and Materiel Command 13

Dr. Kristine Yaffe Northern California Institute for Research and Education (NCIRE) Endophenotypes of Dementia Associated with Traumatic Brain Injury (TBI) in Retired Military Personnel Dr.

14 Dr. Kristine Yaffe Northern California Institute for Research and Education (NCIRE) Endophenotypes of Dementia Associated with Traumatic Brain Injury (TBI) in Retired Military Personnel Dr. Yaffe s team surveyed nearly 300 Veterans at two Veteran retirement homes, which were located in Washington, DC and Northern California. 56% of those surveyed had a history of TBI. TBI was associated with psychiatric symptoms such as depression, anxiety, and post-traumatic stress disorder (PTSD). Veterans with TBI had problems answering orientation questions (a sign of cognitive impairment): 23.3% for the hospitalization group, 18.3% for the TBI group, and 15.4% for non-tbi group. (n=54) We hope our study will improve the healthcare of veterans, especially those with history of TBI, by improving our understanding of how TBI affects cognitive aging and impairments such as Alzheimer s disease. Dr. Kristine Yaffe Study Sites Veterans with TBI were also more likely to have subjective memory complaints (26.7% for TBI hospitalization group, 20.6% for the TBI group, 10.8% for the non-tbi group). (n=156) A total 114 patients reported multiple diagnoses U.S. Army Medical Research and Materiel Command 14 Study Data

Dr. Michael Weiner Northern California Institute for Research and Education (NCIRE) Effects of Traumatic Brain Injury (TBI) and Post-Traumatic Stress Disorder (PTSD) on Alzheimer s disease (AD) in

15 Dr. Michael Weiner Northern California Institute for Research and Education (NCIRE) Effects of Traumatic Brain Injury (TBI) and Post-Traumatic Stress Disorder (PTSD) on Alzheimer s disease (AD) in Veterans using Imaging and Biomarkers from the Alzheimer s Disease Neuroimaging Initiative (ADNI) Use the ADNI machinery to understand TBI and neurodegenerative disease in Vietnam-era Veterans. Study Vietnam-era population to understand the future of veterans returning from OIF/OEF. More than 10,000 Veterans were contacted to form the cohort. Study #1 (2012): Look at Vietnam Veterans (n=195) with signs of TBI and/or PTSD and perform a comprehensive battery of neuroimaging, CSF analyses, and neuropsychological testing. Study #2 (2013): Look at Vietnam Veterans (n=195) with signs of MCI. Both studies are accruing patients across all 19 sites. Sample images showing amyloid negative (left) and positive (right) scans gained from nuclear imaging. Data will become available via the ADNI database. U.S. Army Medical Research and Materiel Command 15

16 Other PI-Reported Findings/Products Evidence for a relationship between cardiovascular health and memory decay in those with amnestic mild cognitive impairment (PI: Fairchild) Putative chromosomal loci associated with AD risk identified (PI: van Broeckhoven) Early/late onset AD genomics identified new genes/variants contributing to AD (PI: Pericak-Vance) Ligands for TBI biomarkers/targets for therapy identified in animal models (PI: Pasinetti) Identified both infiltrating and intrinsic neuroinflammatory mechanisms and inflammatory cell subtypes subserving acute and chronic effects of neurotrauma in animal models (PI: Goldstein) U.S. Army Medical Research and Materiel Command 16

Contact Us www.cdmrp.army.mil http://cdmrp.army.mil/prarp/default.

17 Contact Us U.S. Army Medical Research and Materiel Command 17

Peer Reviewed Alzheimer s Research Program

Peer Reviewed Alzheimer s Research Program US Army Medical Research and Materiel Command Congressionally Directed Medical Research Programs HISTORY The Congressionally Directed Medical Research Programs