Personalized Health(care): more than just targeted medicines 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
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2015 09-14 Precision Medicine 2015, London, Alain van Gool
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Personalized Health(care): more than just targeted medicines
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
My mixed perspectives in personalized health(care)
8 years academia (NL, UK)
(molecular mechanisms of disease)
13 years pharma (EU, USA, Asia)
(biomarkers, Omics)
4 years med school (NL)
(personalized healthcare, Omics, biomarkers)
4 years applied research institute (NL, EU)
(biomarkers, personalized health, nutrition)
A person / citizen / family man
(adventures in EU, USA, Asia)
1991-1996 (PhD)
1996-1998 (post-doc)
2009-2012 (visiting prof)
1999-2007 2007-2009 2009-2011
2011-now
2011-now
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Source: Chakma Journal of Young Investigators. Vol 16, 2009.
Principle of Personalized/Precision/Targeted Medicine
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EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
“But dad, people are more than linear pathways, right ?”
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Optimal Personalized / Precision / Targeted Medicine
Humans are more than linear pathways
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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Personalized health(care)
Is more than ‘just’ targeted medicines
It’s personal !
‘I want to stay healthy.’ ‘If not, how do I get healthy?’
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Partners in personalized health(care)
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Partners in personalized health(care)
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Societal need in efficient personalized health(care)
Source: prof Jan Kremer
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Towards cost effective care, less cure
Alain van Gool, 2nd Precision Medicine Congress, London, 15 Sept 2015
Radboud university medical center
• Nijmegen, The Netherlands
• Mission: “To have a significant impact on healthcare”
• Strategic focus on Personalized and Participatory Healthcare through “the patient as partner”
• Core activities:
• Patient care
• Research
• Education
• 11.000 colleagues
• 52 departments
• 3.300 students
• 1.000 beds
• First academic centre outside US to fully implement EPIC
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Involvement of patients throughout our core activities 1 september 2015: Opening of new curriculum by famous T1DM patient
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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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Patient
Radboud Personalized Healthcare
A significant impact
on healthcare
Molecule
Population
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Cell
Tissue
Subgroup
Alain van Gool, 2nd Precision Medicine Congress, London, 15 Sept 2015
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 studies
EHR-based research
Statistics
Human performance
Data stewardship
Molecule
Flow cytometry
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About 250 dedicated people working in 18 Technology Centers, ~1600 users (internal, external), ~140 consortia www.radboudumc.nl/research/technologycenters/
• Electronic Health Records • Big Data • Best practice
• In vivo • Functional
diagnostics
• iPSC • Organoids
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Alain van Gool, 2nd Precision Medicine Congress, London, 15 Sept 2015
Working with other Technology Networks Region, Netherlands, Europe, world
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About 250 dedicated people working in 18 Technology Centers, ~1600 users (internal, external), ~140 consortia www.radboudumc.nl/research/technologycenters/
Alain van Gool, 2nd Precision Medicine Congress, London, 15 Sept 2015 22
Example of diagnostic glycoprotein biomarker • Rare metabolic disease cases
• Combination glycoproteomics and exome sequencing
• Outcome 1: Explanation of disease
• Outcome 2: Dietary intervention as succesful personalized therapy
• Outcome 3: Glycoprofile transferrin developed and applied as diagnostic test
{Tegtmeyer et al, NEJM 370;6: 533 (2014)}
Genomics Glycomics Metabolomics
{Monique van Scherpenzeel, Dirk Lefeber}
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Discovering new glycoprotein biomarkers
• 1D LC-MS/MS 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:
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Intact protein analysis
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Bottum-up proteomics
Top-down proteomics
Intact complexome analysis as new biomarker?
• Native tissue biopsies
• Isolate intact membrane complexes
• Separate and isolate complexes using native gels
• LC-MS/MS analysis of intact proteins
• Data analysis
Tissue 1 (n=3)
Tissue 2 (n=3)
Subunit
Subunit – tissue 1
Subunit – tissue 2
• Identified protein sequence of subunit • Deduce simulated sequences from database • Determine fit with experimental data
Research Biomarkers Diagnostics
Department of Laboratory Medicine, Radboud univerity medical center Integrated Translational Research and Diagnostic Laboratory, 220 fte, yearly budget ~ 28M euro. Close interaction with Dept of Genetics, Pathology and Medical Microbiology
But … ‘I want to stay healthy. If not, how do I get healthy?’
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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Accelerate translation from research to application
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Gap 3
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Step 2 in Personalized Health(care):
Alain van Gool, 2nd Precision Medicine Congress, London, 15 Sept 2015
Biomarker innovation gaps: some numbers
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 14 Sept 2015: n = 11,805 biomarkers
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Gap 3
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