EuroBioForum 2013 2nd Annual Conference 27-28 May 2013 - Hilton Munich City, Munich, Germany http://www.eurobioforum.eu/2013 ======================================= # NATIONAL PERSPECTIVES # Russia: Introduction into PPPM as a new paradigm of public health care service and an example of the ready-to-use Clinical Model in the Area of Medicine Sergey Suchkov Professor in Medicine and Immunology at Moscow State Medical & Dental University & I.M. Sechenov Moscow Medical Academy ======================================= http://www.eurobioforum.eu

1. Introduction into PPPM as a new
paradigm of public health care services:
from knowledge of the past, through today’s expectations to strive for
the promising reality of tomorrow
Dr Sergey Suchkov, MD, PhD
Professor in Immunology & Medicine
I.M.Sechenov First Moscow State Medical University, Moscow, Russia
A.I.Evdokimov Moscow State Medical & Dental University, Moscow, Russia
EPMA (European Association for Predictive, Preventive and Personalized
Medicine), Brussels, EU
Prof. Dr. Olga Golubnitschaja, PhD
Prof. Dr. Olga Golubnitschaja, PhD
Secretary-General,
European Association for Predictive, Preventive and Personalised
Medicine (EPMA), Brussels, EU

2. Predictive, Preventive and Personalized Medicine
associated with Subclinical Diagnostics

3. GENERAL CONCEPT
www.springer.com
Predictive, Preventive and
Personalized Medicine (PPPM)
as applicable to:
1. Diabetes Care
2. Neurodegenerative Diseases
3. Cancer
4. Cardiovascular
Diseases
5. Reproductive Medicine
&
Paediatrics
6. Body culture & Sport Medicine
2-years
cycle
of 6 issues

6. Predictive Diagnostics as the first step to
Predictive
Diagnostics
Professional
Education
Medicine
Biotechnology
Bioinformatics
Targeted
European
Programm
es
Research
Budgets
Targeted
National &
EU Calls
Knowledge
Transfer
Standardisatio
n
Patenting,
Licenses,
Publications
Industrial
Production
Issue-related
multifunctiona
l
activities
Insurance
Long-lasting
cost-benefit
concept in
favour
of prevention
Laboratory
Diagnostics
Application of
optimal
standardised
approaches
Medical
practice
Preventive
Measures &
Personalised
Patient Treatment
Ethics
Targeted Prevention & Personalised Treatment

12. The Genomewide Association Study
The genomewide association study is typically based on a case–control design in which single-nucleotide polymorphisms
(SNPs) across the human genome are genotyped.
Panel A depicts a small locus on chromosome 9, and thus a very small fragment of the genome.
In Panel B, the strength of association between each SNP and disease is calculated on the basis of the prevalence of each SNP in
cases and controls. In this example, SNPs 1 and 2 on chromosome 9 are associated with disease, with P values of 10−12 and
10−8, respectively.
The plot in Panel C shows the P values for all genotyped SNPs that have survived a quality-control screen, with each
chromosome shown in a different color. The results implicate a locus on chromosome 9, marked by SNPs 1 and 2, which are
adjacent to each other (graph at right), and other neighboring SNPs

22. EPITOPES

23. Common serum cancer-associated
biomarkers & biopredictors (proteomics)

24. Genes and loci implicated into the inheritance of common
malignancies and serve as genomic biomarkers
(according to the risks among heterozygotes)

25. Subclinical (cryptic) latency

26. (1) to predict the likelihood of developing disease;
(2) to estimate the length of the asymptomatic
period;
(3) to provide predictive information about disease
course, severity, and complications;
(4) to serve as a warning to avoid potential disease-
triggering factors;
(5) to identify high-risk individuals who might be
suitable candidates for preventive intervention
trials
Impacts to be assumed for
the practical implementation of
predictive biomarkers and biopredictors
into PPPM

28. This illustrates a functional state of a cell
at the level of metabolism illustrating all
metabolic pathways in the cell at a given
time span

31. • How the human genome has opened up a broad
spectrum of predictive approaches for genetic
diseases by screening individual genes, SNPs,
and haplotypes
• How protein and RNA microarrays are
providing new insight into the nature, subclinical
and clinical courses, and prognosis of certain
ongoing diseases
• How autoantibodies (autoAbs) which now are
known to be present years before the clinical
onset of a number of autoimmune diseases are
being used as predictive biomarkers to enter
high-risk subjects into therapeutic intervention
trials

32. Two key objectives of PPPM are:
(i) detection of subclinical
abnormalities with a selection of
suitable pharmacotherapeutic
targets for the next step of PPPM
protocol, i.e., drug-based
prevention
(ii) drug-based correction of the
abnormalities detected under
preventive measures.

33. PPPM thus uses diagnostic tests of newer
generations, particularly genomic, proteomic, and
metabolomic biomarkers, to individually determine
the health conditions a person is predisposed to and
to reveal the agents of the probable or the already
existing pathological processes.
The predictive branch is mainly designed
to meet the interests of healthy individuals, its
purpose being to determine whether susceptibility to
a particular disease is increased or not.
Preventive medicine is aimed at taking
measures to avoid disease development rather than
cure or treat it on manifestation

34. Personalized medicine proposes the
customization of healthcare, with all decisions and
practices being tailored to the individual patient by the
mutual integration of clinical information, stable and
dynamic genomics, and molecular phenotyping through
bioinformatics.
Personalized medicine generally
promises to result in both higher quality in treatment for
individual patients and in lower costs in healthcare since
patients will be offered only such therapies that are more
effective for them and treatments that will not be safe or
effective will be avoided. Recent advancements in
biomedical and genomic sciences have paved the way to
translate such research into clinical practice and health
policies.

36. Immune
response
genes
HLA-
genes
Nuclear related
metabolism
Mitochondrial
metabolism and
redox metastasis
Ribosome
genes
Ribosome
and
translation
genes
Cytoskeleton
genes
Metal ion
homeostasis
Extracellular
matrix and
adhesion
CD antigens
and plasma
membrane
signals
Human gene co-expression
networks

37. Disease- and
oncogene-related
gene networks

38. Deafness
Cardiomyopathy
OBESITY
Asthma
Leukemia
Colon
cancer
T1D
Ovarian
cancer
GB
Disease-related
gene networks

40. Genes and loci implicated into the inheritance of common
malignancies and serve as genomic biomarkers
(according to the risks among heterozygotes)

41. Deafness
Cardiomyopathy
OBESITY
Asthma
Leukemia
Colon
cancer
T1D
Ovarian
cancer
GB
Disease-related
gene networks

43. Common serum cancer-associated
biomarkers & biopredictors (proteomics)

44. Subclinical (cryptic) latency

45. Subclinical stage
Clinical stage
T1D

46. Первичный
патоген-инфект
(например, ВЭБ)
1. Стадия
индукции РС
(доклиническая
стадия)
2. Стадия
формирования
ПИФАС
3. Стадия начала
воспаления и
демиелинизации
4. Стадия развернутой
клинической картины ПИФАС
1. Subclinical stage
of MS
(symptom-free)
2. A stage to illustrate
PIFAS formation
(symptom-free)
3. A stage to illustrate
starting up of
inflammation
4. A stage to illustrate formation
of clinical manifestations
Brain-Blood Barrier
APC
APC
HLA II
IL4/IL10
IL12
Multiple sclerosis

47. MS: autoimmunity, demyelination and neurodegeneration
Anti-myelin autoAbs and autoreactive CTLs are able to to make
oligodendrocytes and axons damaged in direct and indirect ways to result in
demyelination and neurodegeneration, respectively
Blood
TCR
Neuron
Myelin sheath
Axon
Antimyelin Abs
Damage
Microglia Oligodendrocyte
Damage
Complemen
t
T cell
CTLs
CTLs
CNS

48. Autoantibodies (by green fluorescence)
in human islets exposed to blood from a patient with IDDM1
(the surrounding area is dark because it lacks islets because of еру autoimmune inflammation/insulitis)

49. Major Histocompatibility Complex
(MHC-HLA) in Humans
HLA Class II HLA Class III HLA Class I

50. Differential Roles of Risk Loci in the Pathogenesis of T1D
Many risk loci for
IDDM1 may exert
their effects through
the immune system
(HLA, presumably).
Within the immune
response, these
genes can act at
multiple levels,
affecting the
establishment of the
immune repertoire,
the function of cell
types in the immune
system, or the
regulation of
cellular responses
that can lead to
autoimmunity.

51. Subclinical (cryptic) latency

53. Autoantibodies (by green fluorescence)
in human islets exposed to blood from a patient with IDDM1
(the surrounding area is dark because it lacks islets because of еру autoimmune inflammation/insulitis)

54. Subclinical (cryptic) latency

55. Three different steps are described during cancerogenesi:
initiation is a rapid and irreversible DNA lesion which
occurs after exposure to a carcinogen (physical
carcinogen, chemical carcinogen, viral carcinogen)
promotion is due to prolonged, repetitive or continuous
exposure to substances which maintain and stabilise the
initiated lesion,
progression is the acquisition of non controlled
multiplication properties, independence acquisition, loss of
differentiation, local invasion and metastasis.

56. • The strategy of preventive therapy
should contain, at least, two critical steps.
For chronic autoimmune diseases:
(i) arrest of autoagression; and,
(ii) restoration of structure and functions of the
tissue affected.
For cancerogenesis:
(i) prevention of the initiation and metastatic
activity; and,
(ii) restoration of structure and functions of the
tissue affected.

57. • Prevention of the initiation of the cancer process involves the
protection of cells from carcinogenic agents like tobacco, benzol,
various chemical products, radiation, and so on). Prevention is
dictated by knowledge acquired through human epidemiological
studies as well as experimental cancers in animals.
• Preventing the promotion of the cancer process also involves
protecting the organism from various products and situations, like
alcohol, tobacco, viruses, local irritation processes, and so on).
Prevention results from the same type of epidemiological and
experimental studies. Knowledge of other diseases linked to
developing cancers (such as genital infections or hereditary
syndromes) also facilitates cancer prevention.
• Preventing the progression of cancer is possible through the
same studies but also by active, well designed policies for the
screening of pre-cancerous lesions and small cancers, when policies
are applicable.

58. • The strategy mentioned can be
accomplished by:
•gene therapy, or
•stem cells technologies.

59. • System approach to the formation of an innovative
infrastructure regarding predictive and preventive
algorithms is an ultimate approach that will contribute
to the modernization of the world healthcare services
drastically. Our challenge is that the new guidelines
should create the robust juristic and economic
platforms for advanced medical services utilizing the
cost-effective models of risk assessments followed
by tailored preventive treatments focused on the
precursor stages of chronic diseases. Recently
developed economical models clearly demonstrate
the efficacy of PPPM, if introduced as the integrative
medical approach into the healthcare services.

60. • Individuals to be under regular
monitoring that helps to detect
pathological shifts at subclinical
stages of a disease have a higher life
expectancy and are able-bodied up
to 8–15 years more than those under
traditional treatment. This means that
the society saves more than
US$20,000–40,000 per person
annually.

61. • In general, we see the following main obstacles to
the advancement of PPPM:
• the scientific challenges (a poor
understanding of molecular mechanisms or a lack of
molecular biomarkers, for example);
• the economic challenges (poorly
aligned incentives), and
• operational issues in public healthcare
systems.
The operational issues can often be largely resolved
within a particular stakeholder group, but correcting the incentive
structure and modifying the relationships between stakeholders
is more complex

62. The true era of PPPM, while perhaps
decades away, is impacting the pharmaceutical
and healthcare industries today.
The Saint Trinity, in particular,
• translational research,
• biomarker-based studies and
• careful patient segmentation in
clinical trials,
have led to successes such as new biomarker-
based drugs; drugs with companion diagnostics
and highly targeted therapies.

63. Future
Neurology
Antibody-associated
proteolysis in
surveillance of
autoimmune
demyelination:
clinical and
preclinical issues
“Antibody proteases
can be considered to
be a promising
molecular tool in
monitoring [multiple
sclerosis] patients…”
Alexander Gabibov,
Mihail Paltsev &
Sergey Suchkov

64. Dmitry Kostyushev,
Ivan Tsarev,
Dmitry Gnatenko,
Mikhail Paltsev,
Sergey Suchkov
Open J Immunology,
2012, Vol.1, No.3, 80-86
Myelin-associated
serological targets as
applicable to diagnostic
tools to be used at the
subclinical and transient
stages of MS progression

65. Who should be screened ?
 Should screening include the general
population, or rather first-degree relatives
of patients, genetically prone HLA groups?
Those special groups may benefit more
from the screening compared to the general
population. Accordingly, testing high-risk
groups may change the positive diagnostic
or predictive value of the panel tests used.

66. When should individuals
be screened?
 The best age for screening varies in
different diseases. For example,
while cancer-associated biomarkers
or diabetes-associated antibodies
appear by 3-5 years of age, thyroid
antibodies uncommonly appear
before 20 years of age.

67. Which biomarkers
should be screened for?
 Different biomarkers appearing in
the same diseases have different
diagnostic and predictive values as
individual screening test, as well as
in combination.

68. How should the screening
be performed?
 Specificity and sensitivity of different
laboratory assays must be
considered.
How should we interpret
changes found outside of genes?
 No answer yet…

69. Core question:
Who should be informed?
 Once biomarkers have been found, a
risk of future disease is established.
This information may have great
implication regarding one’s future,
and thus its distribution should be
handled with great care. Should
family members be informed,
especially taking into account their
associated risk?

70. How should we effectively communicate
the results to patients in ways that will
improve health without inducing neurosis?
 No comments.
Should one be informed to expect a disease for
which, at least currently, there is no cure ?
 No answer yet.

71. Should employment authorities be notified?
Should such information be available to all
caring physicians?
Should military authorities be informed? Or
should one be obligated to inform
insurance companies?
More crucial questions and
ethical issues
be considered :

72. EPMA-World Congress 2011
September 15th19th, Bonn, Germany

74. Creation and setting up an international youngers’ research
and clinical team in the area of PPPM and allied fields under
the aegis of:
EPMA (Brussels)
:
Moscow State Medical & Dental University
Russian Academy of Sciences
National Research Center “Kurchatov’s Institute”
National Center “Higher School of Economy”

75. 75
EPMA-World
Congress
Bonn, 2011

77. 77
The First Anglo-Russian Students’ Workshop
on PPPM and Translational Medicine
Lancaster University
4th September 2012
Location: TR1/TR2 Gordon Manley building
Chairs: Professors Frank Martin, PhD (UK)
Director, Environmental and Biophotonics Center, and
Chairman, Dept for Biochemistry, Lancaster University, UK
Professor Sergey Suchkov, MD, PhD (Russia)
Dept of Pathology, School of Pharmacy, I.M.Sechenov First
Moscow State Medical University, and Dept of Clinical
Immunology, Moscow State Medical & Dentistry University,
First Vice-President and Dean, School of PPPM, University of
World Politics and Law, Moscow, Russia

78. 78

80. PPPM is driving key changes in the biopharmindustry
The true era of personalized medicine, while perhaps decades away, is impacting the pharmaceutical and
healthcare industries today. Most notably, this vision is impacting the landscape of how clinical research and
trials are conducted. Translational research, biomarker-based studies and careful patient segmentation in clinical
trials, have led to successes such as new biomarker based drugs; drugs with companion diagnostics and highly
targeted therapies. Fundamental to biomarker research is access to quality biospecimens that have been
extensively annotated with clinical, molecular and patient data. While many organizations have invested heavily
in the IT infrastructure of biospecimen management, or biobanking, such systems are facing challenges to
effectively drive investigative biomarker-based research

81. We offer and propose:
1. To set up several international research teams in the areas defined
under the aegis of EuroBioForum and EPMA in the topical fields pre-
selected (e.g., T1D, MS, cancer, etc.) to accelerate investigations and
obtaining the productive outcome including basic knowledge,
products to be translated into the medical practice and products
finalized to be marketed and distributed
2. To set up an International Team of professionals on the
interdisciplinary basis to start up developing a new Program in the
Higher Medical and Biomedical Education as applicable to PPPM
and Translational Medicine as High-Tech Tools for Training students,
researchers, clinicians, and biotechnologists to secure the Progress in
the areas mentioned
3. To develop a series of different models of Centers for Medical and
allied Health Services as applicable to PPPM
WHAT CAN WE OFFER?

82. 1. Political support
2. Financial support
3. Assistance in bridging cooperative and
collaborative efforts coming from
particular countries or enthusiastic
individuals
WHAT ARE WE LOOKING FOR?

83. 1. To accent a special attention on:
● most advanced areas of medical research and
● to define subareas to identify existing teams with the best outcome
and
● to set up newer international teams under the aegis of EuroBioForum and EPMA in the
topical fields pre-selected (e.g., T1D, MS, cancer, etc.)
2. To set up an International Team of professionals on the interdisciplinary
basis to start up developing a new Program in the Higher Medical and
Biomedical Education as applicable to PPPM and Translational Medicine
as High-Tech Tools for Training students, researchers, clinicians, and
biotechnologists to secure the Progress in the areas mentioned
3. To develop a series of different models of Centers for Medical and allied
Health Services as applicable to PPPM
TOP 3 recommendations
for achieving tangible results