EuroBioForum 2013 - Day 1 | Sergey Suchkov


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EuroBioForum 2013 2nd Annual Conference
27-28 May 2013 - Hilton Munich City, Munich, Germany



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


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EuroBioForum 2013 - Day 1 | Sergey Suchkov

  1. 1. Introduction into PPPM as a newparadigm of public health care services:from knowledge of the past, through today’s expectations to strive forthe promising reality of tomorrowDr Sergey Suchkov, MD, PhDProfessor in Immunology & MedicineI.M.Sechenov First Moscow State Medical University, Moscow, RussiaA.I.Evdokimov Moscow State Medical & Dental University, Moscow, RussiaEPMA (European Association for Predictive, Preventive and PersonalizedMedicine), Brussels, EUProf. Dr. Olga Golubnitschaja, PhDProf. Dr. Olga Golubnitschaja, PhDSecretary-General,European Association for Predictive, Preventive and PersonalisedMedicine (EPMA), Brussels, EU
  2. 2. Predictive, Preventive and Personalized Medicineassociated with Subclinical Diagnostics
  3. 3. GENERAL CONCEPTwww.springer.comPredictive, Preventive andPersonalized Medicine (PPPM)as applicable to:1. Diabetes Care2. Neurodegenerative Diseases3. Cancer4. CardiovascularDiseases5. Reproductive Medicine&Paediatrics6. Body culture & Sport Medicine2-yearscycleof 6 issues
  4. 4. Predictive Diagnostics as the first step toPredictiveDiagnosticsProfessionalEducationMedicineBiotechnologyBioinformaticsTargetedEuropeanProgrammesResearchBudgetsTargetedNational &EU CallsKnowledgeTransferStandardisationPatenting,Licenses,PublicationsIndustrialProductionIssue-relatedmultifunctionalactivitiesInsuranceLong-lastingcost-benefitconcept infavourof preventionLaboratoryDiagnosticsApplication ofoptimalstandardisedapproachesMedicalpracticePreventiveMeasures &PersonalisedPatient TreatmentEthicsTargeted Prevention & Personalised Treatment
  5. 5. The Genomewide Association StudyThe 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 incases and controls. In this example, SNPs 1 and 2 on chromosome 9 are associated with disease, with P values of 10−12 and10−8, respectively.The plot in Panel C shows the P values for all genotyped SNPs that have survived a quality-control screen, with eachchromosome shown in a different color. The results implicate a locus on chromosome 9, marked by SNPs 1 and 2, which areadjacent to each other (graph at right), and other neighboring SNPs
  6. 6. EPITOPES
  7. 7. Common serum cancer-associatedbiomarkers & biopredictors (proteomics)
  8. 8. Genes and loci implicated into the inheritance of commonmalignancies and serve as genomic biomarkers(according to the risks among heterozygotes)
  9. 9. Subclinical (cryptic) latency
  10. 10. (1) to predict the likelihood of developing disease;(2) to estimate the length of the asymptomaticperiod;(3) to provide predictive information about diseasecourse, severity, and complications;(4) to serve as a warning to avoid potential disease-triggering factors;(5) to identify high-risk individuals who might besuitable candidates for preventive interventiontrialsImpacts to be assumed forthe practical implementation ofpredictive biomarkers and biopredictorsinto PPPM
  11. 11. This illustrates a functional state of a cellat the level of metabolism illustrating allmetabolic pathways in the cell at a giventime span
  12. 12. • How the human genome has opened up a broadspectrum of predictive approaches for geneticdiseases by screening individual genes, SNPs,and haplotypes• How protein and RNA microarrays areproviding new insight into the nature, subclinicaland clinical courses, and prognosis of certainongoing diseases• How autoantibodies (autoAbs) which now areknown to be present years before the clinicalonset of a number of autoimmune diseases arebeing used as predictive biomarkers to enterhigh-risk subjects into therapeutic interventiontrials
  13. 13. Two key objectives of PPPM are:(i) detection of subclinicalabnormalities with a selection ofsuitable pharmacotherapeutictargets for the next step of PPPMprotocol, i.e., drug-basedprevention(ii) drug-based correction of theabnormalities detected underpreventive measures.
  14. 14. PPPM thus uses diagnostic tests of newergenerations, particularly genomic, proteomic, andmetabolomic biomarkers, to individually determinethe health conditions a person is predisposed to andto reveal the agents of the probable or the alreadyexisting pathological processes.The predictive branch is mainly designedto meet the interests of healthy individuals, itspurpose being to determine whether susceptibility toa particular disease is increased or not.Preventive medicine is aimed at takingmeasures to avoid disease development rather thancure or treat it on manifestation
  15. 15. Personalized medicine proposes thecustomization of healthcare, with all decisions andpractices being tailored to the individual patient by themutual integration of clinical information, stable anddynamic genomics, and molecular phenotyping throughbioinformatics.Personalized medicine generallypromises to result in both higher quality in treatment forindividual patients and in lower costs in healthcare sincepatients will be offered only such therapies that are moreeffective for them and treatments that will not be safe oreffective will be avoided. Recent advancements inbiomedical and genomic sciences have paved the way totranslate such research into clinical practice and healthpolicies.
  16. 16. ImmuneresponsegenesHLA-genesNuclear relatedmetabolismMitochondrialmetabolism andredox metastasisRibosomegenesRibosomeandtranslationgenesCytoskeletongenesMetal ionhomeostasisExtracellularmatrix andadhesionCD antigensand plasmamembranesignalsHuman gene co-expressionnetworks
  17. 17. Disease- andoncogene-relatedgene networks
  18. 18. DeafnessCardiomyopathyOBESITYAsthmaLeukemiaColoncancerT1DOvariancancerGBDisease-relatedgene networks
  19. 19. Genes and loci implicated into the inheritance of commonmalignancies and serve as genomic biomarkers(according to the risks among heterozygotes)
  20. 20. DeafnessCardiomyopathyOBESITYAsthmaLeukemiaColoncancerT1DOvariancancerGBDisease-relatedgene networks
  21. 21. Common serum cancer-associatedbiomarkers & biopredictors (proteomics)
  22. 22. Subclinical (cryptic) latency
  23. 23. Subclinical stageClinical stageT1D
  24. 24. Первичныйпатоген-инфект(например, ВЭБ)1. Стадияиндукции РС(доклиническаястадия)2. СтадияформированияПИФАС3. Стадия началавоспаления идемиелинизации4. Стадия развернутойклинической картины ПИФАС1. Subclinical stageof MS(symptom-free)2. A stage to illustratePIFAS formation(symptom-free)3. A stage to illustratestarting up ofinflammation4. A stage to illustrate formationof clinical manifestationsBrain-Blood BarrierAPCAPCHLA IIIL4/IL10IL12Multiple sclerosis
  25. 25. MS: autoimmunity, demyelination and neurodegenerationAnti-myelin autoAbs and autoreactive CTLs are able to to makeoligodendrocytes and axons damaged in direct and indirect ways to result indemyelination and neurodegeneration, respectivelyBloodTCRNeuronMyelin sheathAxonAntimyelin AbsDamageMicroglia OligodendrocyteDamageComplementT cellCTLsCTLsCNS
  26. 26. 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)
  27. 27. Major Histocompatibility Complex(MHC-HLA) in HumansHLA Class II HLA Class III HLA Class I
  28. 28. Differential Roles of Risk Loci in the Pathogenesis of T1DMany risk loci forIDDM1 may exerttheir effects throughthe immune system(HLA, presumably).Within the immuneresponse, thesegenes can act atmultiple levels,affecting theestablishment of theimmune repertoire,the function of celltypes in the immunesystem, or theregulation ofcellular responsesthat can lead toautoimmunity.
  29. 29. Subclinical (cryptic) latency
  30. 30. 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)
  31. 31. Subclinical (cryptic) latency
  32. 32. Three different steps are described during cancerogenesi:initiation is a rapid and irreversible DNA lesion whichoccurs after exposure to a carcinogen (physicalcarcinogen, chemical carcinogen, viral carcinogen)promotion is due to prolonged, repetitive or continuousexposure to substances which maintain and stabilise theinitiated lesion,progression is the acquisition of non controlledmultiplication properties, independence acquisition, loss ofdifferentiation, local invasion and metastasis.
  33. 33. • The strategy of preventive therapyshould contain, at least, two critical steps.For chronic autoimmune diseases:(i) arrest of autoagression; and,(ii) restoration of structure and functions of thetissue affected.For cancerogenesis:(i) prevention of the initiation and metastaticactivity; and,(ii) restoration of structure and functions of thetissue affected.
  34. 34. • Prevention of the initiation of the cancer process involves theprotection of cells from carcinogenic agents like tobacco, benzol,various chemical products, radiation, and so on). Prevention isdictated by knowledge acquired through human epidemiologicalstudies as well as experimental cancers in animals.• Preventing the promotion of the cancer process also involvesprotecting the organism from various products and situations, likealcohol, tobacco, viruses, local irritation processes, and so on).Prevention results from the same type of epidemiological andexperimental studies. Knowledge of other diseases linked todeveloping cancers (such as genital infections or hereditarysyndromes) also facilitates cancer prevention.• Preventing the progression of cancer is possible through thesame studies but also by active, well designed policies for thescreening of pre-cancerous lesions and small cancers, when policiesare applicable.
  35. 35. • The strategy mentioned can beaccomplished by:•gene therapy, or•stem cells technologies.
  36. 36. • System approach to the formation of an innovativeinfrastructure regarding predictive and preventivealgorithms is an ultimate approach that will contributeto the modernization of the world healthcare servicesdrastically. Our challenge is that the new guidelinesshould create the robust juristic and economicplatforms for advanced medical services utilizing thecost-effective models of risk assessments followedby tailored preventive treatments focused on theprecursor stages of chronic diseases. Recentlydeveloped economical models clearly demonstratethe efficacy of PPPM, if introduced as the integrativemedical approach into the healthcare services.
  37. 37. • Individuals to be under regularmonitoring that helps to detectpathological shifts at subclinicalstages of a disease have a higher lifeexpectancy and are able-bodied upto 8–15 years more than those undertraditional treatment. This means thatthe society saves more thanUS$20,000–40,000 per personannually.
  38. 38. • In general, we see the following main obstacles tothe advancement of PPPM:• the scientific challenges (a poorunderstanding of molecular mechanisms or a lack ofmolecular biomarkers, for example);• the economic challenges (poorlyaligned incentives), and• operational issues in public healthcaresystems.The operational issues can often be largely resolvedwithin a particular stakeholder group, but correcting the incentivestructure and modifying the relationships between stakeholdersis more complex
  39. 39. The true era of PPPM, while perhapsdecades away, is impacting the pharmaceuticaland healthcare industries today.The Saint Trinity, in particular,• translational research,• biomarker-based studies and• careful patient segmentation inclinical trials,have led to successes such as new biomarker-based drugs; drugs with companion diagnosticsand highly targeted therapies.
  40. 40. FutureNeurologyAntibody-associatedproteolysis insurveillance ofautoimmunedemyelination:clinical andpreclinical issues“Antibody proteasescan be considered tobe a promisingmolecular tool inmonitoring [multiplesclerosis] patients…”Alexander Gabibov,Mihail Paltsev &Sergey Suchkov
  41. 41. Dmitry Kostyushev,Ivan Tsarev,Dmitry Gnatenko,Mikhail Paltsev,Sergey SuchkovOpen J Immunology,2012, Vol.1, No.3, 80-86Myelin-associatedserological targets asapplicable to diagnostictools to be used at thesubclinical and transientstages of MS progression
  42. 42. Who should be screened ? Should screening include the generalpopulation, or rather first-degree relativesof patients, genetically prone HLA groups?Those special groups may benefit morefrom the screening compared to the generalpopulation. Accordingly, testing high-riskgroups may change the positive diagnosticor predictive value of the panel tests used.
  43. 43. When should individualsbe screened? The best age for screening varies indifferent diseases. For example,while cancer-associated biomarkersor diabetes-associated antibodiesappear by 3-5 years of age, thyroidantibodies uncommonly appearbefore 20 years of age.
  44. 44. Which biomarkersshould be screened for? Different biomarkers appearing inthe same diseases have differentdiagnostic and predictive values asindividual screening test, as well asin combination.
  45. 45. How should the screeningbe performed? Specificity and sensitivity of differentlaboratory assays must beconsidered.How should we interpretchanges found outside of genes? No answer yet…
  46. 46. Core question:Who should be informed? Once biomarkers have been found, arisk of future disease is established.This information may have greatimplication regarding one’s future,and thus its distribution should behandled with great care. Shouldfamily members be informed,especially taking into account theirassociated risk?
  47. 47. How should we effectively communicatethe results to patients in ways that willimprove health without inducing neurosis? No comments.Should one be informed to expect a disease forwhich, at least currently, there is no cure ? No answer yet.
  48. 48. Should employment authorities be notified?Should such information be available to allcaring physicians?Should military authorities be informed? Orshould one be obligated to informinsurance companies?More crucial questions andethical issuesbe considered :
  49. 49. EPMA-World Congress 2011September 15th19th, Bonn, Germany
  50. 50. Creation and setting up an international youngers’ researchand clinical team in the area of PPPM and allied fields underthe aegis of:EPMA (Brussels):Moscow State Medical & Dental UniversityRussian Academy of SciencesNational Research Center “Kurchatov’s Institute”National Center “Higher School of Economy”
  51. 51. 75EPMA-WorldCongressBonn, 2011
  52. 52. 77The First Anglo-Russian Students’ Workshopon PPPM and Translational MedicineLancaster University4th September 2012Location: TR1/TR2 Gordon Manley buildingChairs: Professors Frank Martin, PhD (UK)Director, Environmental and Biophotonics Center, andChairman, Dept for Biochemistry, Lancaster University, UKProfessor Sergey Suchkov, MD, PhD (Russia)Dept of Pathology, School of Pharmacy, I.M.Sechenov FirstMoscow State Medical University, and Dept of ClinicalImmunology, Moscow State Medical & Dentistry University,First Vice-President and Dean, School of PPPM, University ofWorld Politics and Law, Moscow, Russia
  53. 53. 78
  54. 54. PPPM is driving key changes in the biopharmindustryThe true era of personalized medicine, while perhaps decades away, is impacting the pharmaceutical andhealthcare industries today. Most notably, this vision is impacting the landscape of how clinical research andtrials are conducted. Translational research, biomarker-based studies and careful patient segmentation in clinicaltrials, have led to successes such as new biomarker based drugs; drugs with companion diagnostics and highlytargeted therapies. Fundamental to biomarker research is access to quality biospecimens that have beenextensively annotated with clinical, molecular and patient data. While many organizations have invested heavilyin the IT infrastructure of biospecimen management, or biobanking, such systems are facing challenges toeffectively drive investigative biomarker-based research
  55. 55. We offer and propose:1. To set up several international research teams in the areas definedunder the aegis of EuroBioForum and EPMA in the topical fields pre-selected (e.g., T1D, MS, cancer, etc.) to accelerate investigations andobtaining the productive outcome including basic knowledge,products to be translated into the medical practice and productsfinalized to be marketed and distributed2. To set up an International Team of professionals on theinterdisciplinary basis to start up developing a new Program in theHigher Medical and Biomedical Education as applicable to PPPMand Translational Medicine as High-Tech Tools for Training students,researchers, clinicians, and biotechnologists to secure the Progress inthe areas mentioned3. To develop a series of different models of Centers for Medical andallied Health Services as applicable to PPPMWHAT CAN WE OFFER?
  56. 56. 1. Political support2. Financial support3. Assistance in bridging cooperative andcollaborative efforts coming fromparticular countries or enthusiasticindividualsWHAT ARE WE LOOKING FOR?
  57. 57. 1. To accent a special attention on:● most advanced areas of medical research and● to define subareas to identify existing teams with the best outcomeand● to set up newer international teams under the aegis of EuroBioForum and EPMA in thetopical fields pre-selected (e.g., T1D, MS, cancer, etc.)2. To set up an International Team of professionals on the interdisciplinarybasis to start up developing a new Program in the Higher Medical andBiomedical Education as applicable to PPPM and Translational Medicineas High-Tech Tools for Training students, researchers, clinicians, andbiotechnologists to secure the Progress in the areas mentioned3. To develop a series of different models of Centers for Medical and alliedHealth Services as applicable to PPPMTOP 3 recommendationsfor achieving tangible results