Journal of Pharmacogenomics & Pharmacoproteomics

Predictive, preventive and personalized medicine (PPPM) as being an integrative part of healthcare services to move ahead

2^nd International Conference on Predictive, Preventive and Personalized Medicine & Molecular Diagnostics

November 03-05, 2014 Embassy Suites Las Vegas, USA

Sergey S Suchkov

Keynote: J Pharmacogenomics Pharmacoproteomics

Abstract:

The medicine is undergoing a paradigm shift to strive from the diagnosis and treatment for prediction and prevention. And, for sure, any innovations in healthcare services are an important driver to move the new trend forward. A new systems approach to disease to pay its crucial attention on the trend would result in a new branch in the healthcare services, namely, predictive, preventive and personalized medicine (PPPM). The latter is defined as: ??the capacity to predict disease development and influence decisions about lifestyle choices or to tailor medical practice to an individual?? As the baby boomers age, the number of people living with chronic conditions will grow dramatically. For instance, forty six million more Americans are projected to have at least one chronic condition in 2030 than in 2000. Meanwhile, all chronic disorders develop gradually over a period of time to take years for a process to reach a level where it could be diagnosed definitively and treatment initiated properly and in time before changes are irreversible! And, for example, Parkinson?s costs society $27 billion per year in medical bills and lost wages; worldwide, projected cases of Parkinson?s will more than double by 2030! To achieve the practical implementation of PPPM concept, it is necessary to create a fundamentally new strategy based upon the subclinical recognition of biopredictors of hidden abnormalities long before the disease clinically manifests itself. This strategy would give a real opportunity to secure preventive measures whose personalization could have a significant influence on demographics! Two key objectives of PPPM are: (i) detection of subclinical abnormalities with a selection of suitable targets for the next step of PPPM protocol, i.e., drug-based prevention; (ii) drug-based correction of the abnormalities detected under the heading of preventive measures. PPPM is thus a medical model being tailored to the individual and dictates a construction of PPPM algorithms to diagnose, to predict, and to prevent in time! The key benefits of PPPM include new abilities: (i) to detect disease at a subclinical stage, when it is easier and less expensive to treat effectively; (ii) to stratify patients into groups that enable the selection of optimal preventive treatment; (iii) to reduce adverse drug effects by more effective early assessment of individual drug responses; (iv) to improve the selection of new molecular targets for drug discovery; (v) to shift the emphasis from illness to wellness. The first discriminatory step illustrating the PPPM-oriented survey is estimating of the correlation strength between genetic polymorphism and risks of the disease, and subsequent construction of the groups at risks. Those goals can be solved by using of BioChip methodology (each disease has individual fingerprints). As a result, a patient becomes a data carrier, i.e., he/she knows about possible risks of a disease, and the physician can reasonably select of preventive protocol, proceeding from the assays made. Individuals, selected at the first stage, undergo the second phase of the survey, which uses a panel of phenotypic biopredictors. Two examples to illustrate the topic: T1D and MS models. T1D is an chronic autoimmune disease resulting in a destruction of pancreatic beta-cells capable alone of producing insulin, by two autoreactive tools, i.e., cytotoxic T lymphocytes and anti-islet autoAbs. For T1D, about half of the total risk is genetic and about half of that genetic risk is in the HLA region on the chromosome 6 to be used for gene-based predictive testing! Other genes are associated with T1D as well, but their contribution to risks is small. Subclinical stages are also determined by identification of highly-specific proteomic-related biopredictors, i.e., different anti-islet autoAbs whose presence would determine risks for initiating subclinical abnormalities and then result in clinical manifestations of T1D. MS is an autoimmune disorder of the central nervous system resulting in a destruction of neuro-myelin compartment including demyelination, axon loss and development of disability. Most of the studies confirmed the supreme role of the variations within HLA genes, particularly HLA-II DR region as MS gene-related risk factors! The crucial step in the MS evolution is a primary myelin damage which is mediated by cytotoxic anti-myelin autoAbs! A portion of those are autoAbs against myelin-basic protein/MBP endowing with MBP-targeted proteolytic activity (so-called, Ab-proteases). Screening for those could become the next step to secure subclinical diagnosis of MS and to predict the clinical course. The activity of Ab-proteases established markedly differs: (i) between MS patients and healthy controls; (ii) among different disease courses; and would correlate with EDSS scales of demyelination and thus the disability of the patients. The sequence-specificity of Ab-proteases would illustrate a common but specific pattern revealing six sites of preferential proteolysis. Some of those sites are located within the immunodominant and encephalitogenic regions of MBP that are responsible for the induction of severe and aggressive forms of MS or for getting the disease run in a similar way. The other sites are less immunogenic to be responsible for either the induction moderate courses of MS or for maintaining clinically moderate courses. The Ab-proteases were initially registered at the subclinical stages of MS, presumably, presumably demonstrating their defined sequence specificity with low immunogenicity. Meanwhile, apart from MS patients, about 24% of the direct relatives were also seropositive for Ab-proteases but to reveal much lower activity as compared with the patients. Half of those seropositive relatives being monitored for 2 years have been demonstrating stable growth of the activity of Ab-proteases which reached their mid-level indices at a time point when had coincided with the initial occurrence of the primary clinical and MRI manifestations. A unique value of Ab-proteases for monitoring MS at different stages of the disease whilst providing a fantastic tool for predicting demyelination is becoming evident and thus a reality. Moreover, Ab-proteases can be programmed and reprogrammed to directly affect the remodeling of tissues (for instance, myelin). Such functionally valuable tools may thus be designed for the newer drug catalysts to act as preventive therapeutic tools! Just comments and reference to malignant neoplasms: the initiation and progression of tumors depend on the stepwise acquisition of specific functions by cancer cells at both the primary and metastatic sites. Tumor initiation (at subclinical stages) is provided by oncogenic mutations and inactivation of tumor-suppressor genes to be identified by genomic tailoring approach! The initiation of metastasis would have to be predicted by a combination of genomic and proteomic approaches! And newer algorithms to suit the need of making the subclinical diagnosis of tumor are already in progress! It would be extremely useful to integrate data harvesting from different databanks for applications such as prediction and personalization of further treatment. Medical practitioners will be able to thus provide more tailored prevention and treatment programs for their patients resulting in improved patient outcomes, reduced adverse events, and more cost effective use of health care resources. Use of PPPM is categorized into predictive and preventive medicine and personalized treatment optimization. The latter refers to pharmacogenomics which aims to match the best available drug or dose to an individual?s genomic profile. Pharmacogenomics can help to inform a tailored dosage regimen allowing for an improved drug response, while managing the risk adverse reactions. Genomic and proteomic information can be used to tailor prevention and treatment to that individual as well as to make informed choices relating to lifestyle, reproductive matters, screening and preventive treatments. The strategy of the latter of, for instance, chronic autoimmune diseases should contain two critical steps: (i) arrest of autoagression; and, (ii) restoration of structure and functions of the tissue affected. The strategy mentioned can be accomplished by: (i) gene therapy, or (ii) stem cells technologies. Implementation of PPPM requires a lot before the current model ?physician-patient? could be gradually displaced by a new model ?medical advisor-healthy men-at-risk?. This is the reason for developing global scientific, clinical, social, and educational projects in the area of PPPM to elicit the content of the new branch. PPPM consists of a wide variety of tests and tools. The decision to utilize them or not is made at the micro level - depending on the type of intervention it could be ordered by administration of hospitals and infirmaries, laboratories or clinics, by doctors, and sometimes directly by individuals/patients! Each decision-maker values the impact of their decision to use PPPM on their own budget and well-being, which may not necessarily be optimal for society as a whole. For instance, individuals decide to order genomic or proteomic tests, or to ask their physicians to order testing for them. Individuals? decisions to order tests or not depends on individuals? awareness of their options, their attitudes to risks and information, and their perceived gains from information! So, a lack of medical guidelines has been identified by the majority of responders as the predominant barrier for adoption, indicating a need for the development of best practices and guidelines to support the implementation of PPPM! Sharing best practices as well as pharmacoeconomic information across provincial healthcare systems is also likely necessary to support efficient and cost-effective national implementation of PPPM! In addition to the promise of improved patient care and disease prevention, there is potential for PPPM to impact on the cost of health care. Health care costs may be lowered by individual genetic test results and/or by analysis of an individual?s full genome sequence (whole genome sequencing) allowing for screening and the tailoring of drugs and treatments to improve outcomes. These functions all play a role in ensuring more targeted and cost-effective health-care into the future. Let me just comment that equally important is a PPPM-related test?s clinical utility, both in terms of its health and economic implications, when compared to standard healthcare. What is a realistic timeline for the incorporation of PPPM into the practice? Patients and their relatives want interventions that work right now! But this raises many critical questions that must be answered before data from basic research can be routinely incorporated into the daily healthcare delivery. So, coordinated measures to optimize the progress should be wellfocused on solving the accumulating problems in healthcare and the concomitant economic burden that societies across the globe are facing more and more. The reason is predicting the future is not a new calling neither even a new challenge to ask merely for the God?s help! So, no needs for soaring in the heaven! Well, indeed, PPPM offers great and real promise for the future, and next generations will speak about the XXI century as a time, when healthcare services became predictive and preventive, and its outcomes - secured and guaranteed!

Biography :

Sergey S Suchkov was born in 11.01.1957, a researcher-immunologist, a clinician, graduated from Astrakhan State Medical University, Russia, in 1980. He has been trained at the Institute for Medical Enzymology, The USSR Academy of Medical Sciences,National Center for Immunology (Russia), NIH, Bethesda, USA) and British Society forImmunology to cover 4 British university facilities. Since 2005, he has been working as Faculty Professor of I.M. Sechenov First Moscow State Medical University and of A.I.Evdokimov Moscow State Medical & Dental University. From 2007, he is the First Vice-President and Dean of the School of PPPM Politics and Management of the University of World Politics and Law. In 1991-1995, He was a Scientific Secretary-in-Chief of the Editorial Board of the International Journal?Biomedical Science? (Russian Academy of Sciences and Royal Society of Chemistry, UK) and The International Publishing Bureau at the Presidium of the Russian Academy of Sciences. In 1995-2005, he was a Director of the Russian-American Program in Immunology of the Eye Diseases. He is a member of EPMA (European Association of Predictive, Preventive and Personalized Medicine, Brussels-Bonn), a member of the NY Academy of Sciences, a member of the Editorial Boards for Open Journal of Immunology and others. He is known as an author of the Concept of post-infectious clinical and immunological syndrome, co-author of a concept of abzymes and their impact into the pathogenesis of autuimmunity conditions, and as one of the pioneers in promoting the Concept of PPPM into a practical branchof health services.