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The future is nearly here:
Personalized Health(care)
Prof Alain van Gool
VNFKD lustrum congres
21 April 2016
My background in personalized health(care)
8 years academia (NL, UK)
(molecular mechanisms of disease)
13 years pharma (EU...
3 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Consider individual differences in life science research
4
4 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Source: Chakma, Journal of Young Investigators, 16, 2009
Principle of Personalized Medicine
5
• The right drug for right p...
Crash course in molecular biology
6
DNA, protein, cell, tissue, system biology
6 Alain van Gool, VNFKD, Den Haag, 21 Apr 2...
Biomarkers
{Biomarkers definition working group, 2001 }
‘a characteristic that is objectively measured and
evaluated as an...
Example: Personalized medicine in melanoma
B-RAFV600E mutation Strong growth of cell Growth of tumor
• B-RAFV600E cells al...
Personalized medicine in melanoma
Treat patients with
B-RAFV600E mutation Inhibit growth of cell
Patients live longerTumor...
Emerging Personalized / Precision / Targeted Medicine
2010:
5%of drugs in pipeline had companion diagnostic biomarker test...
11 Alain van Gool, Rotary Oss, 3 Mar 2016
Optimal Personalized / Precision / Targeted Medicine
People are more than linear pathways
People are more than linear pathways
Source: Barabási 2007 NEJM 357; 4}
• People are different
• Different networks and in...
Personalized Healthcare in a systems view
14 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
A changing world: Moving to Personalized Health(care)
“The term "personalized medicine" is
often described as providing "t...
Societal need in efficient personalized health(care)
{Source: prof Jan Kremer}
Towards cost effective care, less cure
16 A...
Personal need in efficient personalized health(care)
It’s personal !
‘I want to stay healthy.’
‘If not, how do I get healt...
18 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
My route to Personalized Health(care)
19 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Analogy: TOMTOM
GPS to a location
Amsterdam
Traffic jam
Amsterdam
Route 1 Route 2
= Default Traffic jam near Utrecht Alter...
Personalized Health(care) model
GPS to health
Health
Route 1 Route 2
= Default
First signs of
disease risk
Alternative rou...
Personalized health(care) monitoring as part of our lives
• Monitor on background
• Alert when you are at risk
• Advice wh...
3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. ...
Exponential technological developments
• Next generation sequencing
• DNA, RNA
• Risk analysis and therapy selection
• Mas...
Example 1:
Glycoproteomics by mass spectrometry
• Mass spectrometry analysis of glycoproteins in human plasma
• 0,05 micro...
Glycomics
Intact
glycoproteins
Free glycans
Glycopeptides
500
750
1000
1250
1500
1750
m/z
10 15 20 25 30 35 40 Time [min]
...
Personalized healthcare in rare disease
• Children with rare metabolic disease cases (liver disease and dilated cardiomyop...
www.radboudumc.nl/research/technologycenters
Genomics
Bioinformatics
Animal
studies
Stem
cells
Translational
neuroscience
...
Alain van Gool, VNFKD, Den Haag, 21 Apr 201629
Example 2:
the microbiome
Ottman et al.(2012) Front Cell Infect Microbiol. 2:104
HUMAN GUT MICROBIOTA DIVERSITY
{Source: Frank Schuren, TNO}
30 Alai...
HUMAN GUT MICROBIOME
Roeselers et al., 2012 Pharmacological Research
31 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
DEVELOPMENT OF THE NASOPHARYNGEAL
MICROBIOME IN INFANTS (1)
24 months
Biesbroek et al.
Am. J. Resp. Crit. Care Med.
(2014)...
24 months
DEVELOPMENT OF THE NASOPHARYNGEAL
MICROBIOME IN INFANTS (2)
33 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
LINKING DIAGNOSIS TO TREATMENT
Using a system biology-based integrated screening-development workflow
to test and develop ...
A changing world: Getting digital
35 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
36
Example 3:
New data !
(generators, owners)
36 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Science fiction ?
37 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Science reality
38 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
39 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
39
Personalized advice
Action
Selfmonitor
Cloud
Lifestyle
Nutrition
Pharma...
40 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
DIY monitoring of glucose levels
41
• Measure your brain waves (EEG)
• Recognize conditions for maximal
concentration or relaxation.
• Use device to train....
Translational medicine in personalized healthcare
42 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Laboratory Society
23% chance blond hair
What does my DNA tell me?
3.1% Neanderthaler DNA
43 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Genetic risk lung cancer
→ don’t smoke !
What does my DNA tell me?
No expected adverse reaction
to Warfarin
44 Alain van G...
Need for optimal quality in health biomarker analyses
Test, interpret, advice
“Post-traumatic Test Syndrome” ?
46 Alain va...
Try-outs at REshape Center of Health(care) Innovation
Lucien Engelen
… but not all data is useful data !
3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. ...
2. How much can it change?
50
http://www.thirsk.towntalk.co.uk/events/d/35907/
• People are different
• People change duri...
healthy disease disease +
treatment
From population to individual
Subgroups
100%
Individual
Population
51 Alain van Gool, ...
Personalized health(care) model
Personalized
Intervention
of patients-like-me
Personal thresholds
of persons-like-me
Big
B...
3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. ...
3. What should be the follow-up for me?
Personal profile data
Knowledge
Understanding
Decision
Action
54 Alain van Gool, V...
System biology view needed
55
β-cell Pathology
gluc Risk factor
{Source: Ben van Ommen, TNO}
therapy
55 Alain van Gool, VN...
Personalized effects of Pharma-Nutrition
Double inhibition
56
No inhibition
56 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Explore personalized interventions by Pharma-Nutrition
Higher efficacy / less side effects
57
57 Alain van Gool, VNFKD, De...
Translation is key in Personalized Healthcare !
“I’m afraid you’re
suffering from an
increased IL-1β and
an aberrant miR84...
What’s next?
Simulating YOUR health
Heleen Wortelboer
Herman van Wietmarschen
Jan van der Greef
Esther Zondervan
Wim van H...
What’s next?
Simulating YOUR health + Personalized advice + Feedback
60 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Trends and technologies make it happen NOW
Possibilities with
big data
Do it yourself health
measurements possible
Growing...
View in the (very near) future
62 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
Acknowledgements
Ron Wevers
Jolein Gloerich
Hans Wessels
Dirk Lefeber
Monique Scherpenzeel
Leo Kluijtmans
Lucien Engelen
N...
2016 04-21 Association of Dutch Producers of Children and Diet Nutrition (VNFKD), Den Haag, Alain van Gool
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2016 04-21 Association of Dutch Producers of Children and Diet Nutrition (VNFKD), Den Haag, Alain van Gool

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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.

Veröffentlicht in: Gesundheit & Medizin
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2016 04-21 Association of Dutch Producers of Children and Diet Nutrition (VNFKD), Den Haag, Alain van Gool

  1. 1. The future is nearly here: Personalized Health(care) Prof Alain van Gool VNFKD lustrum congres 21 April 2016
  2. 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. 3 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  4. 4. Consider individual differences in life science research 4 4 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  5. 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. 6. Crash course in molecular biology 6 DNA, protein, cell, tissue, system biology 6 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  7. 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. 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. 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. 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. 11 Alain van Gool, Rotary Oss, 3 Mar 2016 Optimal Personalized / Precision / Targeted Medicine
  12. 12. People are more than linear pathways
  13. 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. 14. Personalized Healthcare in a systems view 14 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  15. 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. 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. 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. 18 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  19. 19. My route to Personalized Health(care) 19 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  20. 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. 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. 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. 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. 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] 24 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  25. 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. 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. 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. 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. 29. Alain van Gool, VNFKD, Den Haag, 21 Apr 201629 Example 2: the microbiome
  30. 30. Ottman et al.(2012) Front Cell Infect Microbiol. 2:104 HUMAN GUT MICROBIOTA DIVERSITY {Source: Frank Schuren, TNO} 30 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  31. 31. HUMAN GUT MICROBIOME Roeselers et al., 2012 Pharmacological Research 31 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  32. 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. 33. 24 months DEVELOPMENT OF THE NASOPHARYNGEAL MICROBIOME IN INFANTS (2) 33 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  34. 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. 35. A changing world: Getting digital 35 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  36. 36. 36 Example 3: New data ! (generators, owners) 36 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  37. 37. Science fiction ? 37 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  38. 38. Science reality 38 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  39. 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. 40 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016 DIY monitoring of glucose levels
  41. 41. 41 • Measure your brain waves (EEG) • Recognize conditions for maximal concentration or relaxation. • Use device to train. DIY brainwave monitoring 41 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  42. 42. Translational medicine in personalized healthcare 42 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016 Laboratory Society
  43. 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. 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
  45. 45. 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
  46. 46. Try-outs at REshape Center of Health(care) Innovation Lucien Engelen
  47. 47. … but not all data is useful data !
  48. 48. 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
  49. 49. 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
  50. 50. healthy disease disease + treatment From population to individual Subgroups 100% Individual Population 51 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  51. 51. 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}
  52. 52. 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
  53. 53. 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
  54. 54. System biology view needed 55 β-cell Pathology gluc Risk factor {Source: Ben van Ommen, TNO} therapy 55 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  55. 55. Personalized effects of Pharma-Nutrition Double inhibition 56 No inhibition 56 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  56. 56. 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
  57. 57. 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
  58. 58. What’s next? Simulating YOUR health Heleen Wortelboer Herman van Wietmarschen Jan van der Greef Esther Zondervan Wim van Hartingsveldt 59 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  59. 59. What’s next? Simulating YOUR health + Personalized advice + Feedback 60 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  60. 60. 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
  61. 61. View in the (very near) future 62 Alain van Gool, VNFKD, Den Haag, 21 Apr 2016
  62. 62. 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

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