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Advancing the Health of an Aging Population
Friends of the NIA Senate Briefing
Richard J. Hodes, M.D., DirectorMarie A. Bernard, M.D., Deputy Director
National Institute on Aging
June 30, 2016
Advances at the NIA: From Bench toBedside to Real-World Practice
World’s Older Population is Growing
He et al. U.S. Census Bureau, International Population Reports, P95/16-1,An Aging World: 2015,
• America’s 65-and-over population is projected to nearly double, from 48 mill to 88 mill by 2050
• Global life expectancy is projected to increase by almost eight years, from 68.6 years in 2015 to 76.2 years in 2050
• The global population of people aged 80 and older is expected to more than triple, growing from 126.5 mill to 446.6 mill by 2050
$200M for PMI
$85M for BRAIN
$350M for AD
• $1.6B for the NIA • 4 percent increases across
all ICs (not counting the $$ above) – 4.2% for the NIA
• All divisions will benefit DBSR DGCG
DAB DN
$32 Billion for the NIH
Difference from FY2006
In Current Dollars: $561.6M Increase
In Constant Dollars: $62.7M Increase
6.3% increaseFY06-FY17
NIA Appropriations FY 2005-2017 PBCurrent versus Constant, FY05 Base Year
06 07 08 09 10 11 12 13 14 15 16 17
Actual 1,036.6 1,045.5 1,051.0 1,079.0 1,108.2 1,100.4 1,121.3 1,040.6 1,171.7 1,197.5 1,598.2 1,598.2
Constant 988.9 957.7 913.3 906.4 897.6 859.4 861.2 779.4 851.8 844.2 1,090.0 1,051.6
700
750
800
850
900
950
1,000
1,050
1,100
1,150
1,200
1,250
1,300
1,350
1,400
1,450
1,500
1,550
1,600
1,650D
olla
rs,
in M
illio
ns
$0.000
$0.200
$0.400
$0.600
$0.800
$1.000
$1.200
$1.400
$1.600
$1.800
2013 2014 2015 2016 2017
Do
llars
(in
bill
ion
s)
Fiscal Year
NIA Appropriations
AD funds
Bench
Bedside
Real world
Bench
Bedside
Real world
St. Sauver, JL et al. (2015) BMJ Open Feb 3;5(2):e006413.
Chronic Kidney Disease
Stroke OsteoporosisCong. Heart
Failure
COPD
Hyperlipid. HTN Depression Diabetes
Arthritis CancerCardiac
ArrhythmiasCAD
Disease Prevalence as a Function of Age
Schizophrenia
Epigenetics
MetabolismInflammation
Damage(Repair)
Stress(Adaptation)
Genetics
StemCells
Immunity
Proteostasis
Arthritis
SarcopeniaCKD
COPD Heart Disease
Immunity
VascularDiseaseNeurological
Disease
Cancer
MacularDegeneration
HearingBiologyof
Disease
Biologyof
Aging
Proteostasis
Epigenetics
MacromolecularDamage
Inflammation
OtherBiology
Metabolism
StemCells
StressResponse
Burch, JB et al. (2014) J Gerontol A Biol Sci Med Sci Jun; 69 Suppl 1:S1-3;Kennedy, BK et al. (2014) Cell 159(4): 709–713.
“Geroscience” is the Convergence of Two Fields of Study
Rapamycin -- ITP
Aspirin – ITP Acarbose – ITP
17-a estradiol -- ITP
Lifespan is Plastic
Ad LibitumRestricted
Calorie Restriction
Intermittent Fasting: A Promising Lead
Brandhorst, S et al. (2015) Cell Metabolism 22, 22(1):86-99.
Intermittent Fasting: A Promising Lead
Brandhorst, S et al. (2015) Cell Metabolism 22, 22(1):86-99.
Stay tuned…more to come on calorie restriction later in the talk
Baker DJ et al. (2011) Nature 479:232
Deleting senescent cells delays age-associated disorders
Basic & Translational Projects in the AD Pipeline
• A consortium to look at how vascular risk factors influence AD – focused on molecular mechanisms
• New translational centers to develop – and share – the next generation of animal models of AD
• A biomarkers consortium to study AD in individuals with Down syndrome
• Discovery and development of novel therapeutics for AD against a wide range of targets –Facilitated by AMP
14
Target Discovery and Preclinical Validation
• Shortens the time between discovery of targets to development of new drugs
• Integrates analysis of large-scale molecular data from human brain samples with network modeling approaches and experimental validation
Number of genes or loci
1990 1995 2000 2005 2010 2015
30
25
20
15
10
5
0
Early Onset genes
Innate immune/Brain inflammatory response
Endocytosis and cellular protein trafficking, including APP trafficking and Aββ processing
Lipid transport/metabolism
Synaptic transmission
Cytoskeletal function, including tau
APPPS 1
PS2APOE
CLU
PICALM
SORL1
BIN1
CD2AP
EPHA
MS4A4A
ABCA7
HLA-DRB5
PTK2B
CASS4
CD33
MEF2cC
NME8
CELF1
TREM2
Genetic Regions of Interest in Alzheimer’s Disease
By Year of Discovery
Confirmed loci with no assigned function:IMPP5D, SLC24A4/RIN5
FERM T2
TRIP 4
MAPT
CRI
Bench
Bedside
Real world
Biomarkers Inform Our Understanding of Alzheimer’s Progression
Jack, CR et al. (2013) Lancet Neurol 12(2):207-16.
Clinical, Cognitive, Structural, Metabolic, and Biochemical Changes years Before AD Symptom Onset
Bateman RJ et al. (2012) N Engl J Med; Aug 30; 367:795-804
Aβ Deposition in Autosomal Dominant ADYears before Expected Clinical Symptoms
Bateman RJ et al. (2012) N Engl J Med; Aug 30; 367:795-804
For example, a family in Colombia that develops AD early is generously working with researchers
Early Intervention is One Goal of NIA’s Alzheimer’s Trials
Fleisher, AS et al. (2012) Lancet Neurology 11(12):1057-65.
Gene Carriers, late 30’s
Beta-amyloid, late 20’s
Dementia onset is in late 40’s
Non-Carriers, late 30’s
NIA’s Alzheimer’s-related Trials Explore Many Different Disease Pathways
• Anti-amyloid trials API-ADAD (Colombia families) DIAN-TU API-APOE4 A4
Adds tau imaging and novel fluid biomarkers to these trials - for tracking
responsiveness to treatment and/or disease
progression
NIA’s Alzheimer’s-related Trials Explore Many Different Disease Pathways
• Anti-amyloid trials API-ADAD (Colombia families) DIAN-TU API-APOE4 A4
NIA’s Alzheimer’s-related Trials Explore Many Different Disease Pathways
• In addition to anti-amyloid therapies, NIA-funded clinical researchers are also studying:
o Compounds that
Prevent loss of nerve connections
Restore function of damaged synapses
Promote new neuron growth
o Dietary and physical activity interventions
o Blood pressure control
o Repurposing of drugs that were not successful for their original indications
In the news…
The company NeurotrophiX is planning a test of a growth factor called LM11A-31
The drug may prevent the activation of degenerative processes and protect nerve cells and their connections
February, 2016
The initial Federal investment…
Successful pre-IND studies supported in large part by the NIA/NIH made possible FDA approval for phase I and IIa human testing• AD Translational
Program • IND (Investigational
New Drug) Toxicology Program
February, 2016
NIA Aging-related Clinical Trials in Process
• Examples include:
–Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE)
–Aspirin in Reducing Events in Elderly (ASPREE)
–Enabling Reduction of Low-Grade Inflammation in Seniors (ENRGISE)-Pilot Study
–Study To Understand Fall Reduction and Vitamin D in You (STURDY)
26
Bench
Bedside
Real world
Randomized Trial of Financial-Incentive Programs for Smoking Cessation
Halpern, SD et al. (2015)NEJM 372(22):2108-17.
“Reward” and “Commitment” participants quit more often than treatment as usual
Systolic Blood Pressure Intervention Trial Primary Outcome
The SPRINT Research Group (2015) NEJM 373(22):2103-16.
SPRINT Study
Improving Inappropriate Antibiotic Prescribing
Both behavioral interventions resulted in lower rates of inappropriate antibiotic prescribing
Meeker, D. et al. (2016) JAMA 315(6):562-570.
Accountable justification Peer comparison
Diet and/or Exercise to Treat Heart Failure With Preserved Ejection Fraction
Kitzman, DW et al. (2016) JAMA 315(1):36-46.
Remember Calorie Restriction?
First human trial of long-term CR on effects on aging-related outcomes
Tested feasibility and safety of two-year CR, and its mechanisms
Comprehensive Assessment of Long-
term Effects of Reducing Intake of
Energy
CALERIE Results
Ravussin, E et al. J Gerontol A Biol Sci Med Sci 2015 Sep;70(9):1097-104.
Participation in Research is Essential!
• NIA, CDC, and ACL collaboration -- Recruiting Older Adults into Research (ROAR)
• Encourages older adults, family caregivers to join studies
• First focus is Alzheimer’s; a toolkit is available at https://www.nia.nih.gov/health/publication/roar-toolkit
• Encourages sedentary older adults to be active every day
• Based on the science
• Includes
– people with chronic health conditions and
– older people who traditionally have not embraced exercise and shows them how to do so safely
-- Putting Research in Action
• Examined the affordability and accessibility of hearing –related services to consumers
• Recommended the expansion of options available with the creation of over-the-counter wearable hearing devices
• Recommended clear guidance and regulatory oversight by the FDA
Hearing Health Care for Adults
National Academies of Sciences, Engineering, and Medicine, 2016.
Sponsors included: CDC, DOD, VA, FDA, Hearing Loss Association of America, NIA, NIDCD
• Get free info on aging, health & Alzheimer’s disease • Learn about research & training opportunities