2015 07-03 Nanonext NL Alain van Gool, Amsterdam
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Transcript of 2015 07-03 Nanonext NL Alain van Gool, Amsterdam
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Implementing Personalized Health(care): the need to bridge fields
Professor of Personalized Healthcare Head Radboud Center for Proteomics, Glycomics and Metabolomics Coordinator Radboud Technology Centers
Head Biomarkers in Personalized Healthcare
Prof Alain van Gool
NanoNextNL Medicine Theme Day 3 July 2015, Amsterdam
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My mixed perspectives in personalized health(care)
8 years academia (NL, UK)
(molecular mechanisms of disease)
13 years pharma (EU, USA, Asia)
(biomarkers, Omics)
3,5 years med school (NL)
(personalized healthcare, Omics, biomarkers)
3,5 years applied research institute (NL, EU)
(biomarkers, personalized health, nutrition)
A person / citizen / family man
(adventures in EU, USA, Asia)
1991-1996 1996-1998 2009-2012
1999-2007 2007-2009 2009-2011
2011-now
2011-now
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Key aspects of personalized health(care)
‘Let’s stay healthy. If not, how to get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
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Consider individual differences in life science research
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Source: Chakma Journal of Young Investigators. Vol 16, 2009.
Principle of Personalized/Precision/Targeted Medicine
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Example: Oncology - Vemurafenib (PLX-4032, Zelboraf)
Key biomarkers: Disease: Melanoma Stratification: BRAFV600E mutation Mechanism: P-ERK Cyclin-D1 Efficacy: Ki-67 18FDG-PET, CT Clinical endpoint: progression-free survival (%)
{Source: Flaherty et al, NEJM 2010} {Source: Chapman et al, NEJM 2011}
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Optimal Personalized / Precision / Targeted Medicine
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EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
System biology approach needed in:
Diagnosis Prognosis Treatment Monitoring
People are complex biological systems
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Personalized health(care), more than pathways only
Source: Barabási 2007 NEJM 357; 4}
• People are different • Different networks and influences • Different risk factors • Different preferences
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Personalized health(care) in a systems view
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A changing world: Personalized Medicine@ USA
“The term "personalized medicine" is often described as providing "the
right patient with the right drug at the right dose at the right time."
More broadly, "personalized
medicine" may be thought of as the tailoring of medical treatment to the individual characteristics, needs, and
preferences of a patient during all stages of care, including prevention,
diagnosis, treatment, and follow-up.”
(FDA, October 2013)
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A changing world: Personalized Medicine @Europe
European Science Foundation 30 Nov 2012
Innovative Medicine Initiative 2 8 July 2013
EC Horizon2020 10 Dec 2013
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Personalized Healthcare @ Radboudumc
People are different Stratification by multilevel diagnosis
+ Patient’s preference of treatment
Exchange experiences in care communities Select personalized therapy
Population
Man
Molecule
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Societal goal of personalized health(care)
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Source: prof Jan Kremer
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Partners in personalized health(care)
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Key aspects of personalized health(care)
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
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Exponential technologies
“The only constant is change, and the rate of change is
increasing”
We are at the knee of the exponential curve
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Demo room
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Exponential developments in biomarker technologies
• Next generation sequencing • DNA, RNA • Risk analysis and therapy selection
• Mass spectrometry
• Proteins, metabolites
• Monitoring of disease and treatment effects
• Imaging • Non invasive images, real time • Spatial view of intact organs and organisms
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Next Generation Sequencing
{Nature, July 17 2014, 511: 344-}
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Mass spectrometry • Example: Glycoproteomics in plasma • Detection of ~12.000 unique deconvoluted monoisotopic masses
per single analysis (> 50% are glycopeptides)
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
Proof of principle study:
Monique van Scherpenzeel, Dirk Lefeber, Hans Wessels, Alain van Gool Translational Metabolic Laboratory, Radboudumc, unpublished data 23 Alain van Gool, NanoNext.NL, 3 July 2015
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Imaging
Slide courtesy of Maroeska Rovers, Peter Friedl, Otto Boerman, Radboudumc
Example: Image-guided surgery: • Use (auto)fluorescence to highlight tumor cells • Specific removal of tumor tissue
• Extend to other imaging modalities in operation room (eg MRI)
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The epigenome
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The microbiome
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‘New’ data
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Personalized advice
Action
Selfmonitor Cloud
Lifestyle Nutrition Pharma
DIY monitoring of vital signs
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• DIY sequence your genome and/or your microbiome genome • at a provider, at a pharmacy, at home
• Take your genome to the doctor • Have a personalized healthcare advice
DIY sequencing
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• Measure your brain waves (EEG)
• Recognize conditions for maximal concentration or relaxation.
• Use device to train.
DIY brainwave monitoring
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DIY blood biomarker analysis
• Measure key biomarkers in one drop of blood at few $ per test panel
• Download data to your smartphone to monitor your own trend
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‘insideables’
‘wearables’
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Try-outs at REshape Center of Health(care) Innovation
Lucien Engelen
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But …
Knowledge and Innovation gap:
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
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Biomarker innovation gaps
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Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Gap 3
1. Imbalance between biomarker discovery, validation and application
2. Many more biomarkers discovered than available as diagnostic test
3. Limited translation to point-of-care devices
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Biomarker innovation gaps: some numbers
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5 biomarkers/ working day
1 biomarker/ 1-3 years
1 biomarker/ 3-10 years
?
Eg Biomarkers in time: Prostate cancer May 2011: n= 2,231 biomarkers Nov 2012: n= 6,562 biomarkers Oct 2013: n= 8,358 biomarkers Nov 2014: n= 10,350 biomarkers
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Gap 3
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Way forward: Open Innovation Networks
Shared R&D in biomarkers:
1. Assay development of (diagnostic) biomarkers
2. Clinical biomarker validation (quantification/confirmation, multicenter)
Leading to standardised clinical applications
(Source model: TNO’s Holst Center)
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Interdisciplinary biomarker validation
Standardisation, harmonisation, knowledge sharing in:
1. Assay development
2. Clinical validation
Biomarker Development Center
Open Innovation Network !
Roadmap Molecular Diagnostics
PPP Grant 4.3M Euro
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www.radboudumc.nl/research/technologycenters
Genomics
Bioinformatics
Animal studies
Stem cells
Translational neuroscience
Image-guided treatment
Imaging
Microscopy
Biobank
Health economics
Mass Spectrometry
Radboudumc Technology
Centers Investigational
products
Clinical trials
EHR-based research
Statistics
Human physiology
Data stewardship
Molecule
Flow cytometry
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Good example of multi-center biomarker validation
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But …
Knowledge and Innovation gap:
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
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Most important in Personalized Healthcare:
Focus on the end user: the patient / citizen
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The route to Personalized Health(care)
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Analogy: TOMTOM
GPS to a location
Utrecht
Amsterdam
Utrecht
Amsterdam
Route 1 Route 2
= Default Traffic jam near Utrecht Alternative route
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Personalized Health(care) model
GPS to health
Risk
Health
Route 1 Route 2
= Default First signs of disease risk
Alternative route
Now
Risk
Health
Now
Health
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Personalized Health(care) model
Analogies:
• Technology enabled
• Personal choice to actively monitor or not
• Success through participation of user
• Monitoring should be on the background; only alert when risk
• Commercial competition of tool builders to standard of market leader(s)
• Implementation as standard in society
GPS to health
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Personalized Health(care) model
Ho
meo
sta
sis
A
llo
sta
sis
D
isease
Time
Disease
Health
Personalized Intervention
of patients-like-me
Big Data
Risk profiles of persons-like-me
Molecular Non-molecular Environment …
Personal profile
Selfmonitoring
Adapted from Jan van der Greef (2013)
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Personalized Participatory Pre-emptive
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Translation is key in Personalized Healthcare !
Personal profile data
Knowledge
Understanding
Decision
Action
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System biologist’s world
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β-cell Pathology
gluc Risk factor
{Source: Ben van Ommen, TNO}
therapy
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Translation is key in Personalized Healthcare !
“I’m afraid you’re
suffering from an
increased IL-1β and
an aberrant miR843
expression”
Adapted from:
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?
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Translation is key in Personalized Healthcare !
Select personalized therapy
Treatment options
Succ
ess
rate
s
Example from Prostate cancer patient guide
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Translation is key in Personalized Healthcare !
Treatment options
Pro’s
Con’s
Select personalized therapy
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Explore personalized interventions by Pharma-Nutrition
Shared Innovation Programs through public-private consortia
Higher efficacy / less side effects
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Interact – Educate – speak each other language
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Interact – Educate – speak each other language
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Acknowledgements
Ron Wevers
Jolein Gloerich
Hans Wessels
Monique Scherpenzeel
Dirk Lefeber
Leo Kluijtmans
Lucien Engelen
Paul Smits
Maroeska Rovers
Nathalie Bovy
Bas Bloem
and many others
www.radboudumc.nl/personalizedhealthcare
www.radboudumc.nl/research/technologycenters
www.radboudresearchfacilities.nl
www.linkedIn.com
www.slideshare.net/alainvangool
Many collaborators
Jan van der Greef
Ben van Ommen
Bas Kremer
Lars Verschuren
Ivana Bobeldijk
Marjan van Erk
Carina de Jongh
Peter van Dijken
Robert Kleemann
Suzan Wopereis
and many others
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And funders
CarTarDis
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