Keynote lecture at the 55-year lustrum conference of the Association of Dutch Producers of Children and Diet Nutrition (VNFKD) to reflect on the use of (specialized) nutrition in personalized healthcare.

1. The future is nearly here:
Personalized Health(care)
Prof Alain van Gool
VNFKD lustrum congres
21 April 2016

2. My background in personalized health(care)
8 years academia (NL, UK)
(molecular mechanisms of disease)
13 years pharma (EU, USA, Asia)
(biomarkers, Omics)
4.5 years med school (NL)
(personalized healthcare, Omics, biomarkers)
4.5 years applied research institute (NL)
(biomarkers, personalized health, nutrition)
1991-1996
(PhD)
1996-1998
(post-doc)
2009-2012
(visiting prof)
1999-2007 2007-2009 2009-2011
2011-now (Senior Scientist Integrator Biomarkers)
2011-now (prof)
2
A person / citizen / family man
Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
2016-now (Scientific lead DTL-Technologies)
2016-now (Head Biomarker Platform)
Professor of Personalized Healthcare
Head Radboud Proteomics Center
Coordinator Radboud Technology Centers

3. 3 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

4. Consider individual differences in life science research
4
4 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

5. Source: Chakma, Journal of Young Investigators, 16, 2009
Principle of Personalized Medicine
5
• The right drug for right patient at right dose at right time
• Molecular biomarkers as key drivers of patient selection
• = Precision medicine or Targeted medicine
5 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

6. Crash course in molecular biology
6
DNA, protein, cell, tissue, system biology
6 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

7. Biomarkers
{Biomarkers definition working group, 2001 }
‘a characteristic that is objectively measured and
evaluated as an indicator of normal biological
processes, pathogenic processes, or pharmacologic
responses to a therapeutic intervention’
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
DNA, RNA proteins biochemicals images
7 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

8. Example: Personalized medicine in melanoma
B-RAFV600E mutation Strong growth of cell Growth of tumor
• B-RAFV600E cells always grow and become cancer cells
• RAF inhibitors will block pathway, block cell growth
and inhibit cancers that have a B-RAFV600E mutation
• 60% of melanoma patients have B-RAFV600E mutation
• Basis for a personalized medicine !
8 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

9. Personalized medicine in melanoma
Treat patients with
B-RAFV600E mutation Inhibit growth of cell
Patients live longerTumors disappearCells stop growing
B-RAFinhibitor
9 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

10. Emerging Personalized / Precision / Targeted Medicine
2010:
5%of drugs in pipeline had companion diagnostic biomarker test
2015:
80%
50%
10 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

11. 11 Alain van Gool, Rotary Oss, 3 Mar 2016
Optimal Personalized / Precision / Targeted Medicine

12. People are more than linear pathways

13. People are more than linear pathways
Source: Barabási 2007 NEJM 357; 4}
• People are different
• Different networks and influences
• Different risk factors
13 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

14. Personalized Healthcare in a systems view
14 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

15. A changing world: Moving to Personalized Health(care)
“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)
15
15 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

16. Societal need in efficient personalized health(care)
{Source: prof Jan Kremer}
Towards cost effective care, less cure
16 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

17. Personal need in efficient personalized health(care)
It’s personal !
‘I want to stay healthy.’
‘If not, how do I get healthy?’
17 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

18. 18 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

19. My route to Personalized Health(care)
19 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

20. Analogy: TOMTOM
GPS to a location
Amsterdam
Traffic jam
Amsterdam
Route 1 Route 2
= Default Traffic jam near Utrecht Alternative route
20 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

21. Personalized Health(care) model
GPS to health
Health
Route 1 Route 2
= Default
First signs of
disease risk
Alternative route
Now
Disease risk
Health
Now
Health
21 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

22. Personalized health(care) monitoring as part of our lives
• Monitor on background
• Alert when you are at risk
• Advice what to do
Examples from car dashboard:
• Empty gas tank
• Traffic jam ahead
22 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

23. 3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
23 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

24. Exponential technological developments
• 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
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
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25. Example 1:
Glycoproteomics by mass spectrometry
• Mass spectrometry analysis of glycoproteins in human plasma
• 0,05 microliter analysis: detection of 100.000 signals in one scan
• ~40.000 peptides of which >80% contain sugar modification
• Diagnose patients and identify new biomarkers
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
Proof of principle study:
{Translational Metabolic Laboratory, Radboudumc, unpublished data}
25 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

26. Glycomics
Intact
glycoproteins
Free glycans
Glycopeptides
500
750
1000
1250
1500
1750
m/z
10 15 20 25 30 35 40 Time [min]
26 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
• Protein glycosylations play a major role in human biology and disease
• Great potential as biomarkers and targets for (nutritional) therapy

27. Personalized healthcare in rare disease
• Children with rare metabolic disease cases (liver disease and dilated cardiomyopathy)
• Combination glycoproteomics and exome sequencing
• Outcome 1: Explanation of disease
• Outcome 2: Dietary intervention as personalized therapy
• Outcome 3: Glycoprofile transferrin developed and applied as diagnostic mass spec test
{Monique van Scherpenzeel, Dirk Lefeber}
27 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

28. 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
28
Technologies don’t come alone

29. Alain van Gool, VNFKD, Den Haag, 21 Apr 201629
Example 2:
the microbiome

30. Ottman et al.(2012) Front Cell Infect Microbiol. 2:104
HUMAN GUT MICROBIOTA DIVERSITY
{Source: Frank Schuren, TNO}
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31. HUMAN GUT MICROBIOME
Roeselers et al., 2012 Pharmacological Research
31 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

32. DEVELOPMENT OF THE NASOPHARYNGEAL
MICROBIOME IN INFANTS (1)
24 months
Biesbroek et al.
Am. J. Resp. Crit. Care Med.
(2014) 190(11):1283-92
32 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

33. 24 months
DEVELOPMENT OF THE NASOPHARYNGEAL
MICROBIOME IN INFANTS (2)
33 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

34. LINKING DIAGNOSIS TO TREATMENT
Using a system biology-based integrated screening-development workflow
to test and develop new nutrients with desired effects on microbiota
In silico modelsIn vivo data In vitro model
New nutritient products
(or combinations)
34 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

35. A changing world: Getting digital
35 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

36. 36
Example 3:
New data !
(generators, owners)
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37. Science fiction ?
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38. Science reality
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39. 39 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
39
Personalized advice
Action
Selfmonitor
Cloud
Lifestyle
Nutrition
Pharma
DIY monitoring of vital signs

40. 40 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
DIY monitoring of glucose levels

41. 41
• Measure your brain waves (EEG)
• Recognize conditions for maximal
concentration or relaxation.
• Use device to train.
DIY brainwave monitoring
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42. Translational medicine in personalized healthcare
42 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Laboratory Society

43. 23% chance blond hair
What does my DNA tell me?
3.1% Neanderthaler DNA
43 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

44. Genetic risk lung cancer
→ don’t smoke !
What does my DNA tell me?
No expected adverse reaction
to Warfarin
44 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

46. Need for optimal quality in health biomarker analyses
Test, interpret, advice
“Post-traumatic Test Syndrome” ?
46 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

47. Try-outs at REshape Center of Health(care) Innovation
Lucien Engelen

48. … but not all data is useful data !

49. 3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
49 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

50. 2. How much can it change?
50
http://www.thirsk.towntalk.co.uk/events/d/35907/
• People are different
• People change during life
• Internal and external influences
Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

51. healthy disease disease +
treatment
From population to individual
Subgroups
100%
Individual
Population
51 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

52. Personalized health(care) model
Personalized
Intervention
of patients-like-me
Personal thresholds
of persons-like-me
Big
Biomarker
Data
Molecular
Non-molecular
Environment
…
Time
Disease
Health
Selfmonitoring
Adapted from Jan van der Greef, TNO
Personal profile
Personalized health
Personalized medicine
52 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
{See eg Chen … Snyder, Cell 2012, 148: 1293}

53. 3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
53 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

54. 3. What should be the follow-up for me?
Personal profile data
Knowledge
Understanding
Decision
Action
54 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

55. System biology view needed
55
β-cell Pathology
gluc Risk factor
{Source: Ben van Ommen, TNO}
therapy
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56. Personalized effects of Pharma-Nutrition
Double inhibition
56
No inhibition
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57. Explore personalized interventions by Pharma-Nutrition
Higher efficacy / less side effects
57
57 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Explore in Shared Innovation Programs through public-private consortia

58. Translation is key in Personalized Healthcare !
“I’m afraid you’re
suffering from an
increased IL-1β and
an aberrant miR843
expression”
Adapted from:
?
58 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

59. What’s next?
Simulating YOUR health
Heleen Wortelboer
Herman van Wietmarschen
Jan van der Greef
Esther Zondervan
Wim van Hartingsveldt
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60. What’s next?
Simulating YOUR health + Personalized advice + Feedback
60 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

61. Trends and technologies make it happen NOW
Possibilities with
big data
Do it yourself health
measurements possible
Growing market for
wearables
Health costs rise and
prevention is key
Consumers more open to
realtime and tailored feedback
Information
on food on
digital media
is enormous
N=1
Tailored
interventions
are more
effective

62. View in the (very near) future
62 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016

63. Acknowledgements
Ron Wevers
Jolein Gloerich
Hans Wessels
Dirk Lefeber
Monique Scherpenzeel
Leo Kluijtmans
Lucien Engelen
Nathalie Bovy
Paul Smits
Maroeska Rovers
Bas Bloem
the Technology Centers
and many others
www.radboudumc.nl/personalizedhealthcare
www.radboudresearchfacilities.nl
www.radboudumc.nl/research/technologycenters
alain.vangool@tno.nl
alain.vangool@radboudumc.nl
nl.linkedin.com/in/alainvangool
www.slideshare.net/alainvangool
Many collaborators and funders
Jan van der Greef
Ben van Ommen
Ivana Bobeldijk
Lars Verschuren
Marjan van Erk
Peter van Dijken
Heleen Wortelboer
Wessel Kraaij
Peter Wielinga
Ronald Mooij
Suzan Wopereis
Nard Clabbers
and many others
CarTarDis
63 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016