Transcript CAN WE DEVELOP A COHERENT STRATEGIC FRAMEWORK FOR BIOMEDICAL RESEARCH? GLOBAL Public Health Challenges Acute to Chronic Conditions Aging Population Health Disparities Emerging and Re-emerging infectious Diseases Emerging Non.

CAN WE DEVELOP A
COHERENT STRATEGIC
FRAMEWORK FOR BIOMEDICAL
RESEARCH?
GLOBAL Public Health Challenges
Acute to Chronic Conditions
Aging Population
Health Disparities
Emerging and Re-emerging infectious
Diseases
Emerging Non communicable
diseases
Need to Transform Medical Research
in the 21st Century
20th Century
21st Century
Treat disease
when symptoms appear and
normal function is lost
Intervene before symptoms
appear and preserve normal
function for as long as
possible
Did not understand the
molecular and cellular
events that lead to disease
Understanding preclinical
molecular events and ability
to detect patients at risk
Expensive in financial and
disability costs
Orders of magnitude
more effective
Fundamental Roadblocks in
Research and Development
Basic
Research
Examples of
key
roadblocks
Some
opportunities
for
improvement
Biology
Target ID Target Valid.
Validation of
complex
diseases
Biomarkers,
Animal
models,
Systems
biology,
Chemical
genomics
Chemistry
Screening
Optimization
Development
Pre-clinical
Clinical
Insufficient
read-out on
safety and
toxicology
Lack of
standardization
and efficiency of
clinical trials
Biomarkers,
Animal
models,
Data sharing
Biomarkers,
Clinical
training,
Regulatory
harmonization,
Informatics
Ind.
Discov.
What is the NIH Roadmap for Medical
Research?
• A framework of scientific priorities that
the NIH as a whole must address in order
to optimize its entire research portfolio.
• A vision for a more efficient, innovative
and productive system of research into
health, mechanisms of disease, and
related behaviors.
The NIH Roadmap for Medical Research
New Pathways to
Discovery
Research Teams
of the Future
Re-engineering the
Clinical Research
Enterprise
Complexity of Biological Networks
• Multiple levels of
cross-talk between
molecular pathways
• Many molecular
targets part of intricate
signaling networks
•Novel experimental and
theoretical concepts
needed
Complexity of Biological Networks
“All molecules are created
equal, but some are more
equal than others.”
Animal Pharm*
*Adapted from George Orwell’s Animal Farm
Biological Data of the Future
Current
Future
Destructive
Qualitative
Uni-Dimensional
Low Temporal
Resolution
Non-localized
Low data density
Variable standards
Non-Cumulative
Non-Destructive
Quantitative
Multi-Dimensional
High Temporal
Resolution
Spatially resolved
High data density
Common standards
Cumulative
Combining Functional Imaging
with GFP Linked Gene Expression
230 ml/gm
6.2 ml/gm.min
c
c
Vascular volume
0
c
Permeability
0
GFP expression
MatLyLu tumor (430 mm3), capillary marked by c
IN VIVO
CELLULAR
MOLECULAR
IMAGING
Pre-ICMIC Program at JHU-RADIOLOGY
NCI P20 CA86346
MOLECULAR NANOMACHINES
Architecture of an 11,000 kDa
Pyruvate Dehydrogenase Complex
475 Å
J. Milne and S. Subramaniam, National Cancer Institute, NIH
High Field MRI of White Matter Tract Development
in Mouse Embryos
st
ic
White matter reconstruction studies of a mouse brain
at embryonic day 16 (ex vivo)
Solving the “Puzzle”
of Complex Diseases
and Conditions
Obesity: A Worldwide Issue
Cancer
Atheroscleroris
Gallbladder
Disease
Hypertension
Obesity
Health
Risks
Heart
Failure
Kidney
Failure
Stroke
Diabetes
New Discoveries in Obesity Research Using RNA
Interference (RNAi)
Thin
Worm
Normal
Worm
Source: Ashrafi et. al., Nature, Vol. 421, pp. 268-272.
Obese
Worm
Human Genome Project and HapMap
Are Complete: Where Do We Go From Here?
 Plummeting cost of DNA
sequencing
 New discoveries
accelerating revolution of
the practice of medicine
 Genes, Environment,
and Health Initiative
– Identify roots of 10 most
common diseases
– Devise new ways of
monitoring personal
environmental exposures
Advances in Age-related Macular
Degeneration (AMD)
Normal vision
Vision affected by AMD
 AMD is the leading cause of
blindness in people over age
60
 Variations in certain genes
involved in inflammation can
predict the risk of developing
AMD
– 56 % of the unaffected individuals
had a variant that conferred
protection to AMD
– 74 % of those with AMD had no
protective variants
New Discoveries Make it Possible to
“Personalize” Cancer Treatment
Identified 16
informative
genes
Impact:
Test tumor
samples for
mutations in
these genes
 70,000 women do not
have to undergo
chemotherapy
 100,000 women each
year can make a more
informed choice
 Reduces routine cost of
treating these patients
Predict which patients
need chemotherapy
– For each patient year of life
gained, we save ~$8,000
Pharmaco-Genomics:
Managing Human Variability
 Pharmaco-Genetics
Research Network (PGRN)
– National collaboration of
scientists studying the effect
of genes on people's
responses to a wide variety
of medicines
 Pharmaco-Genetics &
Pharmaco-Genomics
Knowedge Database
(PharmGKB)
– Integrated knowledge base
for pharmacogenetics linking
phenotypes and genotypes
http://www.nigms.nih.gov/Initiatives
SCIENTIFIC FOCUS AREAS
Basic
R&D
New Pathways to
Discovery
Fundamental
Translational
Target ID &
Validation
Screening/
Optimization
Preclinical
Clinical
Phases I-III
Practice
Systems biology
Iterative chemistry
Predictive toxicology
Translational
Centers
Animal models
Target identification and validation
Biomarkers
Networks
NECTAR
Pharmacogenetics
Training
Research
Teams of the
Future
Harmonization
of policies
and regulations
Harmonization
Public Trust
Strong Bioethics and Privacy regulations
The Future Paradigm: Transform
Medicine from Curative to Preemptive
Predictive
Personalized
Preemptive
NIH research initiatives and programs
are aiming to transform the practice of
medicine as we know it.
“Meeting World Health Problems:
The Need for Sound Program Planning”
With the true spirit of cooperation, with
the basic understanding of needs, and with
the efforts of enlightened groups
everywhere, we can push forward to new
frontiers of world health and well-being.
Dr. Joseph W. Mountin (1952)
Founder of CDC
NIH
Transforming medicine
through discovery