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The Horizons of Predictive Medicine. Dr Ian Gilham Worldwide Director, Predictive Medicine Glaxo Wellcome Research and Development. What is a diagnostic?. “A device or service that provides specific information on the current health status of an individual”. However………. - PowerPoint PPT Presentation
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1SIMG Florence 4.12.99.ppt
The Horizons of Predictive Medicine
The Horizons of Predictive Medicine
Dr Ian GilhamWorldwide Director, Predictive
MedicineGlaxo Wellcome Research and
Development
2SIMG Florence 4.12.99.ppt
What is a diagnostic?What is a diagnostic?
“A device or service that provides specific information on the current health status of an individual”
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However………...However………...
Newer technologies can be used to determine
Predisposition to future change in health status
Monitoring of health statusSuitability for specific medicines
A better description would be…...
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Predictive MedicinePredictive Medicine
“A device or service that can predict a change in the health status of an individual, either towards the onset of disease or towards the likely response to a therapeutic intervention.”
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PrognosticsSurrogates
What is Predictive Medicine?
What is Predictive Medicine?
Diagnostics
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20th Century20th Century
SYMPTOMS OF DISEASE
DIAGNOSTICS(IVD, IMAGING)
OUTCOME
THERAPEUTICINTERVENTION
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21st Century21st Century
DIAGNOSTICS(IVD, IMAGING)
PREDISPOSITION PROFILING(GENETICS, FUNCTIONAL GENOMICS)
THERAPEUTICINTERVENTION
MONITORING AND PREVENTION(BEHAVIOUR MODIFICATION, SURROGATES, VACCINES ETC)
TREATMENT SELECTION (PHARMACOGENETICS)
TREATMENT MONITORING(THERAPEUTIC RESPONSE, SURROGATES, COMPLIANCE)
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PATIENT-TARGETEDTHERAPIES
INNOVATIVEMEDICINES
PREDICTIVEMEDICINE
Right Medicine
Right Patient
Right Disease
Right Time
Right Dose
Right Response
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The drivers and enablers of Predictive
Medicine
The drivers and enablers of Predictive
Medicine-- Today -- -- Tomorrow --
Diagnosis
Treatment
Prediction
Prevention
Dri
vers
• Payer pressures (governments/insurance firms): more prevention, more effective cures
• Regulator pressure to try to eliminate adverse events
• Demand for better healthcare from the patient• Demand for more accurate healthcare predictions for
the patient• Shareholder expectation of growth - getting better
medicines to the market faster
En
able
rs
• Development of Genetics and Functional Genomics knowledge
• New technologies (e.g. genechips, bioinformatics, molecular diagnostics, etc.)
• New regulation on Intellectual Property Rights, genomic ethics, data protection & consent
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Genetics Diagnostics
TherapeuticsDisease
Management
Health Outcomes
MolecularDiagnostics
In Vitro Diagnostics
Imaging
Monitoring Devices
Predisposition Profiling
Gene Therapy
Population Stratification
VaccinesProteins
Small Molecules
Pharmacoeconomics
Compliance
Therapeutic Intervention
Non-Therapeutic Intervention
Potential areas of interest
Potential areas of interest
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Application of Predictive Medicine
Application of Predictive Medicine
Disease Detection
Disease Intervention
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Susceptibility Gene Strategy
Susceptibility Gene Strategy
Alzheimer Disease
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Human GeneticsHuman Genetics
Over the past two decades, disease genes have been identified for hundreds of rare, inherited diseases that are seen in families
Susceptibility genes underlie common diseases (e.g. diabetes, heart disease, asthma)
To date, only one susceptibility gene linked to a common, polygenic disease (APOE, Alzheimer)
Over the past two decades, disease genes have been identified for hundreds of rare, inherited diseases that are seen in families
Susceptibility genes underlie common diseases (e.g. diabetes, heart disease, asthma)
To date, only one susceptibility gene linked to a common, polygenic disease (APOE, Alzheimer)
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Glaxo Wellcome Genetics Strategy
Glaxo Wellcome Genetics Strategy
To identify susceptibility genes To identify susceptibility genes contributing to the risk and age of onset contributing to the risk and age of onset of common diseases with high unmet of common diseases with high unmet needneed
Identify the 20-30 most relevant genes Identify the 20-30 most relevant genes for specific diseases, using genetics and for specific diseases, using genetics and genomic tools. genomic tools.
Focusing to find specific susceptibility Focusing to find specific susceptibility genes is the artgenes is the art
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Genetics Research - Outcomes
Genetics Research - Outcomes
DiseaseSegmentation
Definition ofunderlyingDisease
MechanismsRight
medicinesto RightPatient
Gene Analysis
Gene ExpressionAnalysis
Development of “mechanism-based”medicines
Development of Diagnosticsto detect Disease segment
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Changing technology will accelerate susceptibility gene
discovery
Changing technology will accelerate susceptibility gene
discovery
Database of wellcharacterised
patients &their DNA
Database of geneticpolymorphism and
high capacity resequencing technology
(in development)
Geneticepidemiology
Gene - Diseaseassociations
Current genomic screening technology (today)
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Alzheimer costs a lot today…...
Alzheimer costs a lot today…...
2.3 million Alzheimer cases in the US4% of 75 year olds8.5% of 80 year olds28.5% of 90 year olds
360,000 new US cases each yearUS costs estimated at $90bn annually
Source: Reuters 1998
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Alzheimer will cost more tomorrow….
Alzheimer will cost more tomorrow….
1992 - 7.0% of population over 75 years old
2051 - 13.6% of population over 75 years old
Estimated 7.5m to 14.3m Alzheimer sufferers in the US by 2050
Source: Prevention of Alzheimer Disease JAMA (262): p251
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APOE in Alzheimer disease - a
susceptibility Gene
APOE in Alzheimer disease - a
susceptibility Gene
60 65 70 75 80 85 90
1.0
0.8
0.6
0.4
0.2
0
Pro
port
ion
of
each
g
en
oty
pe
un
aff
ect
ed
Age at onset
2/3
2/43/3
3/4
4/4
Mean age of onset of Alzheimer disease as a function of the inheritance of the five common APOE genotypes
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Significance of APOESignificance of APOE
Predictive Medicine
Drug Discovery
21SIMG Florence 4.12.99.pptSource: Reiman et al NEJM 334 p752
Symptomatic Alzheimer Disease
22SIMG Florence 4.12.99.pptSource: Reiman et al NEJM 334 p752
APOE4 Homozygotes
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APOE as a Predictive Medicine Tool in
Alzheimer Disease
APOE as a Predictive Medicine Tool in
Alzheimer Disease
Value in assigning more accurate diagnoses, not simply whether a patient is APOE4 “positive” or APOE4 “negative”
If a patient is cognitively impaired, and fits the current clinical diagnosis of possible AD, the diagnostic accuracy goes from 60-70% to >95% if the patient carries an APOE4 allele
Value in assigning more accurate diagnoses, not simply whether a patient is APOE4 “positive” or APOE4 “negative”
If a patient is cognitively impaired, and fits the current clinical diagnosis of possible AD, the diagnostic accuracy goes from 60-70% to >95% if the patient carries an APOE4 allele
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APOE as a potential diagnostic
Considerations
APOE as a potential diagnostic
ConsiderationsRigorous test validation Role of APOE in other neurological
conditionsValue of a diagnostic in the
absence of an effective therapyOutcomes analysisRegulatory considerations
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Significance of APOESignificance of APOE
Predictive Medicine
Drug Discovery
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Disease Mechanism and Target Identification
Strategy
Disease Mechanism and Target Identification
StrategyCreate a transgenic animal with the
only difference being the human polymorphism isoform associated with disease
Determing differences in appropriate organsDifferential Gene ExpressionProteomicsOthers
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APOE GeneCalling Study
APOE GeneCalling Study
APOE knock out (KO) mouse = normal
ID “rescue” genes in APOE KO mouse (compensate for APOE loss)
VS.
NORMALAPOE KO
AD “Rescue” Genes
GeneCalling
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APOE GeneCalling Study
APOE GeneCalling Study
APOE3 form = normalID mechanism whereby APOE4
AD
VS.
APOE4APOE3
Other AD Genes
GeneCalling
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APOE in Alzheimer Disease
APOE in Alzheimer Disease
True ValueIn Treating
Disease
TherapyPredictive
Testing
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SummarySummary
Today
Diagnosis
Treatment
Prediction
Prevention
Tomorrow
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What are the consequences to the Global Healthcare?
What are the consequences to the Global Healthcare?
How will the Healthcare look in the 21st Century?
The gate keeping role of patient-specific information
Selection of intervention method and timing
An integrated health management approach
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SummarySummary
Clear trends in Genetics and Predictive Medicine will lead to broader options in therapeutic interventions
Traditional healthcare paradigm will be impacted by new technologies and ever-expanding disease knowledge
An integrated approach could be a key feature of 21st Century Healthcare