Day 1 :
Keynote Forum
Claude Prigent
Institute of Genetics and Development of Rennes, France
Keynote: Is Aurora-A kinase as good biomarker and why?
Time : 10:35 AM
Biography:
Claude Prigent is a Director of Research CNRS and Head of the Cell Cycle team, IGDR. He has been elected as an Associate Professor at the University Laval, Quebec, Canada. After completing his Post-doc in the DNA repair filed under the direction of Thomas Lindahl at the ICRF in London he has been working on mitosis trying to understand how this cell cycle stage was control by phosphorylation. He focused his activity on the Aurora-A kinase and cancer.
Abstract:
Aurora-A serine threonine kinase is a key player in cell cycle controls and essential for the progression through mitosis. It was found over-expressed in many human cancers. A gain of activity was proved to favour chromosome instability and carcinogenesis in mice. More importantly its over-expression was also reported to lead to resistance to drugs such as microtubule poisons used in chemotherapy. Additionally a loss of Aurora-A activity leads to uncontrolled stem cells proliferation at the origin of cancers in Drosophila and presumably in mice too. Aurora-A kinase has been a priority target for the development of inhibitors to be used in cancer treatment. Using a chemical-genetic approach, we investigated the effects of a specific inhibition of Aurora-A kinase during cell cycle progression, in particular during mitosis, in normal conditions but also in the presence of taxol or nocodazole. At the contrary to previous reports, we found that Aurora-A kinase activity was essential to arrest the cells in mitosis in response to taxol or nocodazol. An inhibition of Aurora-A in the presence of these drugs clearly leads to abortive mitosis, and formation of polyploidy cells.
Keynote Forum
Trevor G Marshall
Autoimmunity Research Foundation, USA
Keynote: Biomarkers face an increasingly complex human biology
Time : 10:05 AM
Biography:
Trevor G Marshall graduated from the University of Adelaide, South Australia, in 1974. He taught at the Institute of Technology in Lae, Papua New Guinea, Curtin University and the University of Western Australia, before moving to California in 1982. His Doctoral thesis, ‘Insulin metabolism in Diabetes,’ was accepted by the University of Western Australia in 1985. He is currently Director of the Autoimmunity Research Foundation in California. He has won US FDA Rare Disease Designations for minocycline and clindamycin in the treatment of sarcoidosis. He is a Fellow of the European Association for Predictive, Preventive and Personalised Medicine (Brussels) and a member of the International Expert Council, Community of Practice: Preventative Medicine (Moscow).
Abstract:
Human biology, or at least the understanding of the complexity of human biology, has exponentiated since the turn of the century. Previously it was thought that the human Genome, or at least its Transcriptome subset, expressed around 20,000 proteins. Yet the Human Proteome is currently estimated to be between 250,000 and 1 million proteins. Add to that the 42,000 components of the human Metabolome which have already been identified, and the process of identifying clinically useful biomarkers is becoming very difficult indeed. Our focus has been on yet another level of complexity, the Microbiome, understanding its biomarker contribution by both transcriptional and post-translational mechanisms. While studying the action of microbiome components on the VDR Nuclear Receptor we came to realize that the biomarkers loosely called “Vitamin D†were actually steroid transcriptional-factors, rather than “vitamins.†When we published this it seemed as though the whole world had descended on our shoulders. Clinical Medicine just didn’t want to know that what it thought was a biomarker for health was actually a biomarker for disease. Even today, now that the prosective studies are coming in, few appreciate the complexity of properly interpreting the “Vitamin D†biomarkers. Here we propose that TNF-alpha is also a compromized biomarker. The discovery that TNF-alpha release in the spleen is controlled primarily by the brain, and that brain immune activity is affected by the electrosmog which nowadays surrounds us, necessarily changes the way that this biomarker needs to be studied and interpreted.
- Track 1: Types of Biomarkers
Track 7: Techniques to Maximize Biomarker Identification
Chair
Martin Weber
Austrian Institute of Technology GmbH, Austria
Co-Chair
Jan Voskuil
Everest Biotech Ltd., UK
Session Introduction
Martin Weber
Austrian Institute of Technology, GmbH, Austria
Title: DNA methylation biomarkers for Lung cancer: From tissue based discovery to cell free DNA methylation testing
Biography:
Martin Weber has completed his Ph.D. at the age of 29 at the Center for Molecular Biology (ZMBH) in Heidelberg/Germany. He then served in different positions at QIAGEN GmbH (Hilden/Germany) for more than 17 years, heading the corporate research and innovation group in his last position at the company. Since 2012 he is the Head of the Molecular Diagnostics business unit at AIT Austrian Institute of Technology, the biggest non-university research institute in Austria. He has published more than 20 papers and patent applications.
Abstract:
Disease-specific alterations of DNA methylation patterns are frequently found in cancer and are currently considered to be suitable biomarkers. These alterations are optimal biomarkers for early detection and disease monitoring when detectable in cell-free DNA. We have developed a multiplexed methyl sensitive restriction enzyme (MSRE) qPCR protocol allowing up to 96 parallel qPCR reactions out of 400µl patient’s plasma. The method was applied on 1) a panel of 35 methylation markers discovered in lung tissue by a targeted DNA methylation micro-array and 2) 63 candidate markers derived form genome wide methylation analyses using Illumina-Methylation450K-Beadchip. To test the feasibility for differential diagnosis via cell free DNA methylation testing, multivariate classification using MSREqPCR data from marker panel 1) enabled differentiation of Lung cancer (n=348; Adeno-Ca: n=100, Squamous cell-Ca: n=100, Small cell-Ca: n=100, and Large cell Ca: n=48) versus cancer-free controls (n=332) with an AUC of 0.81-0.91 depending on the lung cancer entity. Using panel 2) a total of 204 serum and plasma samples (lung cancer, n=33; fibrotic Interstitial lung disease - ILD, n=68; COPD, n=42; healthy, n=61) were tested. ROC analysis revealed an AUC of 0.91 for lung cancer, 0.815 for fibrotic ILD, 0.73 for COPD, and 0.828 for all diseases versus healthy controls. Additionally a set of independent cancer and normal samples could be classified on basis of the top 4 markers (HOXD10, PAX9, PTPRN2 and STAG3) showing an AUC 0.85. Based on 2 discovery studies Lung-cancer biomarkers suitable for minimal invasive diagnostics using multiplexed DNA methylation measurement from 10ng circulating cfDNA have been defined. Both marker-sets and the MSREqPCR approach will be the basis for further validation to improve minimal invasive diagnostics. Moreover, this study confirms that our strategy is suitable for qualifying tissue derived DNA-methylation markers for liquid biopsy testing.
Marsha A Moses
Harvard Medical School, USA
Title: Mining the human urinary proteome biomarker discovery for human cancer and its metastases
Biography:
Marsha A. Moses is the Julia Dyckman Andrus Professor at Harvard Medical School and the Director of the Vascular Biology Program at Boston Children's Hospital. She received a Ph.D. in Biochemistry from Boston University and completed a National Institutes of Health postdoctoral fellowship at Boston Children's Hospital and MIT. She is the recipient of a number of NIH and foundation grants and awards. Dr. Moses was elected to the Institute of Medicine of the National Academies of the United States in 2008 and to the National Academy of Inventors in 2013.
Abstract:
The Moses Laboratory has had a long-standing interest in identifying and characterizing the biochemical and molecular mechanisms that underlie the regulation of tumor growth and progression. Dr. Moses and her laboratory have discovered a number of inhibitors of tumor neovascularization that function at both the transcriptional and translational level, some of which are in preclinical testing. Named a pioneer in the field of Biomarker Medicine by the Journal of the National Cancer Institute, Dr. Moses established a Biomarker Discovery Initiative in her laboratory to complement these studies. This has led to the identification and validation of panels of noninvasive biomarkers that can predict disease status and stage of patients with a variety of human cancers. These cancer biomarkers have been validated using our extensive IRB-approved biorepository. They are sensitive and specific markers and have been shown to be useful in monitoring the therapeutic efficacy of cancer drugs as well. Given that Dr. Moses has focused on the urinary proteome, all of these biomarkers are noninvasive. A number of these urine tests are included in her significant patent portfolio and have been made commercially available. Dr. Moses and her group have utilized two experimental approaches to discover these biomarkers, the first being a biologically-driven (candidate biomarker) approach and the second being an unbiased global proteomics approach. Examples of each of these discovery approaches and some of the biomarkers that were discovered and validated will be presented.
Jan Voskuil
Everest Biotech Ltd., UK
Title: The road from discovery to therapy through the use of antibodies
Biography:
Jan Voskuil is a Molecular cell biologist completed his Ph.D. in Amsterdam (NL), and he had postdoc positions at Stanford (US), and at Oxford (UK). He switched from academia to industry through a leading position at the CNS drug discovery company Synaptica. He subsequently gained experience in GLP-regulatory environments at CROs in Oxfordshire and Cambridgeshire (UK). Thanks to his combined academic and commercial background together with his technical and people skills as the Chief Scientific Officer he has put Everest Biotech (UK) on the global map with the highest quality standard. Its antibodies are increasingly recognized as alternatives to unfit monoclonal antibodies.
Abstract:
Any reagent specific to a particular protein will owe its success to a series of quality assurances ranging from quality of biological samples, the reagent’s validation, validated statistic methods and analysis and clinical end point. Alternatives to antibodies, like aptamers and antibody-derived recombinant molecules, have come to light. However, together with monoclonal antibodies, the screening to find the right reagent is expensive and time consuming, and the epitope the reagent binds to needs to be identified afterwards. Problems regarding specificity are not necessarily solved by the switch from monoclonal antibody to such alternatives. Although the demand of having unlimited access to the exact same reagent will be best met once no longer dependent on hybridomas and animals, until this moment arrives, limiting access to fit-for-purpose monoclonal antibodies slows down medical progress. Then using peptide-specific polyclonal antibodies becomes a short-term option. Such reagents are being designed by the choice of the epitope as unique for the species or tissue type upfront without having to concern about cross-reactivity of the reagent. Yet, full reagent validation in the required platform remains compulsory, and depending on the type of application, the correct dilution needs to be determined for minimal non-specific background.
In the next decade, more and more aptamers and recombinant antibody derivatives will be used as an alternative to monoclonal antibodies but before then the peptide-generated polyclonal antibodies will be used more often while the troublesome other types of polyclonal antibodies are avoided.
Biography:
Scott Marshall, PhD, is Managing Director of Biomarker and IVD Analytics at Precision for Medicine. He has extensive industry experience in a leadership role, consulting in the pharmaceutical, biotechnology, and biodefense industries, specializing in the analytical component of personalized medicine, biomarker R&D, analytical methods, and strategy development, as well as medical device/diagnostic development.
Abstract:
The future of healthcare will be transformed by flexible frameworks designed to discover complex signals in rich datasets through the merger of predictive genomic analytics and systems biology. Smart machine learning algorithms designed to incorporate information about molecular and cellular systems can revolutionize our ability to discover complex hierarchical genomic effects driving disease pathogenesis or severity and treatment response patterns. To meet modern research demands, Precision for Medicine has engineered PATH™ to provide a secure, scalable, cloud-based solution for predictive genomic analytics and an intuitive graphical user interface for interactive data visualization and exploration. This case study will show the power of using a novel combination of machine learning algorithms with a systems biology based approach for identifying genes and the subsequent exonic regions driving prognosis for patients with lung squamous cell carcinoma (SQCC). PATH™ will be applied on 553 lung SQCC patients with survival outcomes and RNA-Seq exon-level mRNA expression data obtained from The Cancer Genome Atlas. This webinar will focus on two of the PATH™ Analytics Platform’s suites: • PATH™ Select: A novel predictive analytics engine, built on a combination of machine learning algorithms fused with a systems biology approach provides for high-throughput feature selection • PATH™ Explore: A secure, web based data visualization suite enables real-time, “what-if” data exploration to accelerate research and support decision making Big data has the potential to enable a precision medicine focused drug development process, resulting in increased benefit-risk profiles for patients with a particular biomarker profile and smaller, shorter clinical trials. Navigating the process from biomarker discovery to a companion or complementary diagnostic requires that researchers get the support necessary to make sense of big data being generated in NGS pipelines. Ultimately, it will be demonstrated how a cloud-based solution powered by a predictive analytics engine and an intuitive, user interface driven by interactive graphics can deliver to the needs of precision medicine programs.
Sharon Nofech Mozes
University of Toronto, Canada
Title: Prediction of local recurrence in ductal carcinoma in situ: Clinical validation of DCIS Score
Biography:
Nofech-Mozes obtained her medical degree from Tel Aviv University, Israel. She completed breast and gynecologic pathology fellowships at the University of Toronto, Canada. Dr. Nofech-Mozes is an Associate Professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto. She is the breast pathology lead in Sunnybrook. She is a member of the institutional Research Ethics Board. Her main research interest is ductal carcinoma in situ. Dr. Nofech-Mozes authored or coauthored more than 55 peer reviewed manuscripts, including provincial guidelines for hormone receptor testing in breast cancer and biomarkers synoptic report for the CAP.
Abstract:
The Ontario DCIS population-based study identified women with pure DCIS from 1994-2003. Clinical validation of DCIS Score (DS) (Rakovitch, SABCS 2014) showed prediction of risk of an ipsilateral local recurrence (LR). Centrally reviewed pathology for: focality, size, grade, subtype, comedo necrosis & clear margins, (CM=no ink on tumor) will be presented. The DS was obtained by quantitative RT-PCR. Cox modeling was used to determine the relationship between independent covariates, DS (hazard ratio (HR)/50 units) & LR. DCIS Score was evaluated in 718 women w/ DCIS tx with BCS alone (571 w/ CM). With a median follow-up of 9.4 years, 100 BCS alone w/ CM cases developed LR (44 DCIS, 57 invasive). In the primary analysis, among 571 pts treated by BCS alone with CM the continuous DS was significantly associated with LR in ER+ pts (HR 2.26; 95% CI 1.41, 3.59; P=0.001) and in all pts (HR 2.15; 95% CI 1.43, 3.22; P=<0.001). The results of univariable and multivariable analyses, hazard ratios for factors associated with in situ and distance local recurrence will be presented. DCIS Scores were widely distributed within each subgroup defined by the clinical and pathology characteristics. For DCIS pts treated with BCS alone the DCIS Score, focality, tumor size and histologic subtype provide independent LR information. Patients with low DCIS score and non-multifocal disease may be considered for BCS alone.
Biswendu B Goswami
FDA Center for Food Safety and Applied Nutrition (Retired), USA
Title: Virus identification: Development of methods in the post-PCR antiviral therapy
Biography:
Biswendu B Goswami received his PhD in Biochemistry degree from the University of Calcutta (Kolkata) in 1975, followed by a post-doctoral fellowship from CSIR, India for two years. He came to USA on a post-doctoral fellowship in the laboratory of the Late Prof. Ernest Borek. He worked also as a Research Associate at Georgetown University Medical Center at Washington D.C. He later joined The United States Food and Drug Administration, and was in charge of the Virology laboratory at the Center for Food Safety, until he retired in 2011. He has published more than 45 research articles and book chapters.
Abstract:
The necessity for rapid methods of virus identification arose from the fact that human diseases caused by viruses range from self-limiting to deadly infections. Each of these virus species have dozens of genotypes. The number of human infections reported each year has made viruses a major public health problem world-wide. Food-borne viruses in particular, are causing more and more localized epidemics that are very difficult to trace and identify, and have been associated with high morbidity and increasingly high mortality. Currently, other than common disinfection guidelines and a few synthetic antivirals, there are no effective control measures available. Development of immunologic protocols remain time consuming and expensive. Detection of viruses are mostly being done by PCR or immunological detection in blood or other body fluids. However, current available PCR methods are inadequate to identify the virus strain and emergence of new genotypes that may no longer be controlled by an established active or passive immunotherapeutic protocol agent. Here we deal with molecular techniques to circumvent these obstacles.
Biography:
N S Neki is working as Professor of Medicine, Govt. Med. College/ Guru Nanak Dev Hospital, Amritsar. He is recipient of 4 FRCP’s from Edinbourgh, Glasgow, London, and Ireland. He is Visiting Professor, Institute of Cardiovascular Sciences, University of Mannitoba St. Bonniface Hospital, Winnipeg, Canada as well as Visiting Professor, School of Medicine, Health and Pharmacy, University of Durham, UK. He has 205 publications to his credit in reputed journals. He has delivered lecture in Mannitoba Association of Asian Physicians, GIMLI, Canada, Sept7-9, 2012. He is Associate Editor, Section Editor and Editorial Board Member of various national and international journals. He was awarded Fellowship of European Society of Cardiology 2014, Barcelona, Spain and is member of American college of cardiology and American Heart Association. He has 9 oration awards to his credit.
Abstract:
A biomarker is a substance used as an indicator of a biological state. With the increase in prevalence of coronary artery disease, early diagnosis and management of acute coronary syndromes and myocardial infarction (MI) as well as risk stratification and prognostication is of utmost importance. Hence there is need of cardiac biomarkers. Cardiac biomarkers are very useful in a non diagnostic ECG which is observed in 50% cases. Amongst various cardiac biomarkers, CPK-MB and Troponins (T & I) are the markers of choice for detecting myocardial dysfunction since other cardiac markers may be elevated in muscle injury, kidney and liver disease. Troponins are commonly used in the diagnosis of acute coronary events and myocardial damage because of high specificity and sensitivity, thus detecting myocardial injury in patients presenting late. They have replaced CPK-MB for diagnosis of MI. The levels of Troponin are increased within 4-8 hours after the onset of chest pain reaching peak concentration in 12-24 hours and remaining elevated for 4-10 days following acute MI. Although no ideal biomarker exists, yet Troponins fulfill most of the criteria of ideal biomarker. However false elevation of Troponins level may occur in pulmonary embolism, non-ischemic cardiac disorders, sepsis, stroke , trauma , internal bleeding, renal failure, hypovolemia, atrial fibrillation, congestive heart failure, myocarditis etc. So one should be aware of these non-ACS conditions. However abnormal values may be interpreted carefully in the proper clinical interest.
Paul Tempst
Memorial Sloan Kettering Cancer Center, USA
Title: Aminopeptidase activities as biomarkers for cancer
Biography:
Paul Tempst, PhD, has 40 years of experience in protein chemistry, biochemistry, molecular biology and mass spectrometry, including as a Postdoc at Caltech, Junior Faculty at Harvard Medical School, and Professor at Memorial Sloan Kettering Cancer Center and at the Weill Graduate School of Cornell University (New York). He leads a proteomics and biomarker discovery team and has collaborated worldwide to identify novel proteins and protein complexes: PDGF, Prions, NFkB, IkB, NF-E2, PI3K, mTOR, Raptor, p27kip, SNAREs, Mediator, Elongator, Polycomb, RSC, SWI/SNF, Exosome, and Histone deacetylases, methylases, demethylases and ubiquitinating complexes. His lab pioneered the evaluation and use of protease activities as biomarkers for cancer.
Abstract:
Human cells produce 550 proteases with widely different functions. Several have been implicated in cancer where they promote both tumor progression and suppression. Our group has discovered exopeptidase activities in previous onco-peptidomic studies that provided class discrimination between patients with different types of solid tumors. Owing to their relatively low levels in serum on an immense proteome background, exopeptidases have rarely been detected in proteomic screens and therefore not evaluated as potential biomarkers. Our cancer biomarker discovery studies have therefore focused on proteolytic activities as opposed to steady state levels. We have developed fluorescence-based, quantitative assays to selectively measure activities of 10 individual aminopeptidases (APs) in blood serum or plasma without the need for any sample pre-fractionation or pre-treatment. These tests are uniquely suited to probe altered AP activities in cancer patients and can be applied in parallel to analyze large numbers of samples, followed by multivariate statistical analysis. So far, we have discovered a 2-plex AP activity pattern that allowed prediction of breast cancer biopsy outcome (malignant or benign) with good sensitivity and specificity, as well as a 2-plex pattern that correlates well with high risk (i.e., short survival) of patients with castrate resistant metastatic prostate cancer. Future studies will focus on development and large-scale screens of aminopeptidase and other protease activity assays as markers in a variety of tumor types. If effective functional cancer biomarker panels materialize, it would have a major clinical impact for non-invasive cancer detection and prognostication.
Shrikant Mane
Yale University School of Medicine, USA
Title: Recent advancements in mendelian genomics and data management at the Yale center for genome analysis.
Biography:
Dr. Mane completed his PhD at the age of 28 years from The University of Bombay and postdoctoral studies from The Johns Hopkins University School of Medicine. He is the director of Yale Center for Genome Analysis, one of the most scientifically productive and accomplished Genome Centers in the world. He has published more than 100 papers in reputed journals and has been serving as an ad hock reviewer of several journals. He is currently one of the principle investigators of a $12 million grant from NIH/NHGRI to establish The Yale Center for Genome Analysis.
Abstract:
The Yale Center for Genome Analysis (YCGA) is a state-of-the-art DNA Sequencing Center launched in 2010 to provide an open access centralized facility for services, equipment and expertise required for carrying out large-scale sequence analysis studies (http://ycga.yale.edu/). Since its inception in 2010, YCGA has emerged as one of the leaders in the field of identification of disease associated genetic factors. Our group foresaw scientific opportunities for the development and use of exome sequencing in Mendelian genetics and was the first to develop the method for exome capture on the Nimblegen/Roche platform. We were also the first to demonstrate the biological utility of exome sequencing for clinical diagnostic applications. Currently, YCGA is a part of the NHGRI supported Yale Center for Mendelian Genomics that uses NGS and computational approaches to discover the genes and variants that underlie Mendelian conditions. In the last four years, the use of next-gen sequencing has led to the publications of >150 articles in peer reviewed journals, including >30 in high profile journals such as Science, Nature, Cell, New England Journal of Medicine and Nature Genetics reporting new variants in various disorders, including hypertension, autism, several types of cancers, Gaucher disease, skin disorders, and cortical malfunctions, all using exome analysis. The presentation will focus on recent discoveries in Mendelian disorders made at YCGA, its computer infrastructure and the current challenges and solutions developed for data analysis and management.
Wancai Yang
University of Illinois at Chicago, USA
Title: Epigenetic alterations in colitis-associated colorectal cancer
Biography:
Wancai Yang is a Professor of Pathology and Dean of the School of Basic Medical Sciences at Xinxiang Medical University, China, and an Adjunct Professor of University of Illinois at Chicago, Chicago, Illinois, USA. He was trained as a pathologist in China and received postdoctoral training in Rockefeller University and Albert Einstein Cancer Center, New York, USA. He has published more than 70 papers in high-impact journals about his research on colorectal and esophageal cancers. He has also been serving as grant reviewer, article reviewer and editorial board members of reputed journals.
Abstract:
Besides the canonical and non-canonical Wnt pathway to colorectal cancer, chronic colitis is strongly associated with colorectal cancer formation. However, the mechanisms of colitis develops and how chronic colitis progress to malignance is not clear. Using a unique mouse model, we have demonstrated that the mice with targeted disruption of the intestinal mucin gene Muc2 spontaneously develop chronic inflammation at colon and rectum at early age, whose histopathology was similar to ulcerative colitis in human. After 3 months of age, the Muc2-/- mice develop colonic and rectal adenocarcinoma accompanying severe inflammation. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments) in Muc2-/- mice. Based on relevance to cytokines and cancer, some miRNAs were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. We further characterized one of the most changed miRNA – miR-27a. We found that miR-27a was significantly reduced in colorectal cancer tissues and colorectal cancer cell lines, and that the reduced miR-27a was associated with distant metastasis and colorectal cancer clinical pathological stages. Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3. In vivo, miR-27a inhibited colon cancer cell growth in tumor-bearing mice. Bioinformatic and systemic biological analysis predicted several targets of miR-27a, among them SGPP1 and Smad2 were significantly affected, and interestedly, miRNA-associated cytokines were also significantly increased in Muc2-/-mice. SGPP1 and Smad2 were negatively correlated with miR-27a in human colorectal cancer tissues and cancer cell lines. More studies from the Muc2-/- mice showed disorder of gut microbiota. The disorder of gut microbiota could result in genetic mutations, epigenetic alterations, and activation of oncogenic signaling, in colorectal epithelial cells, leading to colitis development, promoting malignant transformation and mediating colorectal cancer metastasis.
Lynnette R. Ferguson
University of Auckland School of Medical and Health Sciences, New Zealand
Title: Assessing the efficacy of dietary interventions in prostate cancer susceptibility and progression by the use of biomarkers
Biography:
Lynnette Ferguson completed a D. Phil at Oxford University (UK), and then returned to Auckland University for Post-Doctoral studies.She has worked as part of the Auckland Cancer Society Research Centre since it was first established, in 1979.Lynnette currently holds this as a joint appointment with the University Department of Nutrition. She has supervised more than 30PhD or MSc students published more than 350 papers in reputed journals, and serves as an editorial board member of several respected journals.
Abstract:
New Zealand has one of the world’s highest rates of prostate cancer incidence. Both the likelihood of disease occurrence and its’ rate of progression are affected by diet. The dubious ethics of dietary intervention followed by waiting for a cancer endpoint are well illustrated by the example of selenium. The SELECT (Selenium and Vitamin ECancer Prevention Trial)trial began in 2001, and recruited large numbers of men to see if one or both of these dietary supplements could help prevent prostate cancer. In 2014, analysis showed that men who started the trial with high levels of selenium, doubled their risk of developing a high-grade prostate cancer by taking the selenium supplement tested (selenomethionine). This is highly relevant to New Zealand, since our soils are low in this element. Our own studies have used various biomarker endpoints to assess the efficacy of a different form of selenium (selenised yeast), especially in men who show low blood selenium levels, to reduce the probable disease risk and rate of progression. The meaning, relevance and efficacy of these endpoints will be compared.
Rinu Sharma
Guru Gobind Singh Indraprastha University, India
Title: Diagnostic implications of altered miRNA profiles in esophageal cancer
Biography:
Dr. Rinu Sharma has obtained her master's degree in Biotechnology and Ph.D. in Biochemistry from All India Institute of Medical Sciences. She is a faculty in School of Biotechnology, Guru Gobind Singh Indraprastha University, India. She has published more than 20 papers in reputed international journals some of which are the first reports. Her current areas of interest are identification of non-invasive blood based biomarkers for early diagnosis of esophageal cancer and functional analysis of significantly altered genes using gene silencing and proteomic approaches.
Abstract:
The asymptomatic nature of esophageal cancer (EC) at early stages of the disease results in late clinical presentation leading to poor prognosis and limited success of therapeutic modalities. Despite advancement in diagnostic and therapeutic strategies, the five year survival rate of the disease still remains less than 20%. This is primarily due to lack of sensitive and specific markers for early diagnosis and monitoring response to therapy for this disease. Hence, there is a pressing need for establishment of novel non-invasive or minimally-invasive biomarkers for esophageal cancer. Growing evidence suggests importance of alteration in microRNA (miRNA) expression in development and progression of cancer. Moreover, presence of miRNAs in various body fluids such as serum, plasma, saliva, and urine, has opened a new era of disease research. . Our group is interested in deciphering the clinical and functional significance of miRNAs in esophageal cancer. We have evaluated the expression of a panel of miRNAs in tissues as well as sera of esophageal cancer patients. The analysis revealed significant dysregulation of these miRNAs in EC tissues as compared to matched distant nonmalignant tissues. Receiver operated curves generated for these miRNAs showed that they possessed significant diagnostic potential individually and as a panel. Moreover, relative levels of circulating miRNAs in serum significantly distinguished EC patients from normal controls with a high sensitivity. The present paper will discuss the individual as well as collective diagnostic potential of these miRNAs and their targets in EC.
Arjumand Warsy
King Saud University, Saudi Arabia
Title: DNA repair gene polymorphisms as genetic markers of breast cancer
Biography:
Arjumand Warsy completed her PhD at the age of 27 years from Nottingham University, and postdoctoral studies from Birmingham University, UK. She has been working at King Saud University from 1977 and is Professor of Biochemistry at College of Science, King Saud University, Riyadh, Saudi Arabia. She has published over 230 papers in reputed journals and is serving as an editorial board member of Arab Journal of Forensic Sciences & Forensic Medicine. She has presented over 280 papers at different conferences/symposia. She has received several awards and was awarded the President’s Award at King Saud University in 2008.
Abstract:
Breast cancer is the most common cancer in females both in the developed and developing countries and constitutes a major cause of cancer related morbidity and mortality. The etiology of breast cancer is multifactorial, where genetic, environmental, and lifestyle factors interact to produce the malignant transformation. Interest in single nucleotide polymorphism (SNPs) in different genes has gained considerable momentum and many genes have been investigated on the lookout for specific genetic markers of cancer. DNA repair genes constitute one such group. Defects in DNA repair pathways have been shown as predisposing factors to the development of several types of cancers. We investigated several SNPs in RAD51, XRCC2, XRCC4, XRCC3 involved in DNA double-strand break (DSB) repair mechanisms and ERCC1 and ERCC4 in involved in Nucleotide-excision repair (NER), using TaqMan genotyping assay, PCR-RFLP and sequencing. rs861539 and rs1799794 in XRCC3, rs1800067 in ERCC4, rs1801321 and rs2619681 in RAD51 were significantly associated with breast cancer in Saudi females. We compared the results in ER+/ER-, PR+/PR-, HER+/HER-, females with different stages of the disease and different age of disease development and identified several associations. When the results were compared with results reported in different populations and ethnic groups, significant differences were identified. This paper will cover a comprehensive overview of DNA repair mechanisms and the defects which have been observed linked to breast and other cancers in different populations and will also discuss the pros and cons of using SNPs as markers of breast cancer.
- Workshop - Biomarkers of novel generations to secure diagnostic, predictive, prognostic, therapeutic and preventive goals: A way to get the academia, faculty, biopharma and society united
Chair
Sergey Suchkov
I.M.Sechenov First Moscow State Medical University, Russia
Co-Chair
Trevor G Marshall
Autoimmunity Research Foundation, USA
Session Introduction
Sergey Suchkov
I.M.Sechenov First Moscow State Medical University, Russia
Title: PPPM as a model of healthcare services to operate biomarkers of newer generations to monitor clinical and subclinical stages of chronic inflammatory conditions of autoimmune origin
Biography:
Sergey Suchkov graduated from Astrakhan State Medical University and was awarded with MD. In 1985, Suchkov obtained his Ph.D. He is the PhD student of the I.M. Sechenov Moscow Medical Academy and Institute of Medical Enzymology, USSR Academy of Medical Sciences, Moscow, Russia. In 2001, Suchkov finished the PostDoc Research Fellowship Program and maintained his Doctor Degree at the National Institute of Immunology, Russia. From 1987 through 1989, Dr. Suchkov was a senior Researcher, Lab of Developmental Immunology, Koltzov Institute of Developmental Biology, USSR Academy of Sciences to deal to developmental immunology. From 1989 through 1995, Dr. Suchkov was being a Head of the Lab of Clinical Immunology and Immunobiotechnology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004, Dr. Suchkov was being a Chairman of the Department for Clinical Immunology, Moscow Clinical Research Institute (MONIKI) and the Immunologist-in-Chief of the Moscow Regional Ministry of Health. At present, Dr Sergey Suchkov, MD, PhD, is Professor in Immunology, Department of Pathology, School for Pharmacy, I.M. Sechenov First Moscow State Medical University, Dean of the Department (Faculty) of The PPPM Development, and the First Vice-President of the University of World Business, Politics and Law and Secretary General, United Cultural Convention (UCC), Cambridge, UK.
Abstract:
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). 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. 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 groups at risks. As a result, a patient or a person-at-risk would become a data carrier, 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 biomarkers. Etiopathogenesis of autoimmune diseases (in particular, at its subclinical stage) is still poorly known despite in-tensive research of mechanisms of autoaggression. Two examples of autoimmune conditions areT1D (type 1 diabetes) and MS (multiple sclerosis).T1D is a chronic autoimmune disease resulting in a destruction of pancreatic beta-cells capable alone of producing insulin. About half of the total risk is genetic and to be used for gene-based predictive testing and getting the proper genomic biomarkers identified. Subclinical stages are determined by identification of proteomic-related biopredictors, i.e., anti-islet auto Abs whose presence would determine risks and time points for initiating subclinical abnormalities. MS is an autoimmune disorder of the central nervous system (CNS) resulting in a destruction of neuro-myelin compartment and de-velopment of disability. Most of the studies confirmed the supreme role of the variations within HLA genes as MS gene-related risk factors and the proper genomic biomarkers identified. The crucial step in the MS evolution is a primary myelin damage which is mediated by cytotoxic anti-myelin auto Abs. A portion of those are auto Abs against myelin-basic protein/MBP en-dowing with MBP-targeted proteolytic activity (so-called, Ab-proteases). Screening for those biomarkers could become the next step to secure subclinical diagnosis of MS and to predict the clinical course. The information harvested can be used to tailor prevention. The strategy of the latter of, for chronic autoimmune diseases should contain two critical steps: (i) Arrest of auto-agression; and, (ii) restoration of structure and functions of the tissue affected. The strategy mentioned can be accomplished by: (i) gene therapy, (ii) immune-mediated therapy, and/or (iii) stem cells technologies.
Trevor G Marshall
Autoimmunity Research Foundation, USA
Title: Post-infectious autoimmune syndrome (PIFAS) as a predictive and a diagnostic factor to monitor chronic diseases of infectious and autoimmune origin (CDIO)
Biography:
Trevor G Marshall graduated from the University of Adelaide, South Australia. His Doctoral thesis has been titled with ‘Insulin metabolism in Diabetes’. Currently, he is Director of the Autoimmunity Research Foundation in California. He has won US FDA designations for Minocycline and Clindamycin in the treatment of Sarcoidosis. He is a Fellow of the European Association for Predictive, Preventive and Personalized Medicine, Brussels and a Member of the International Expert Council, Community of Practice: Preventative Medicine, Moscow.
Abstract:
Even though chronic inflammatory disease can comprise 70% of a nation's health budget, its molecular mechanisms have remained elusive. Without a clear pathogenic description, the available treatments for autoimmune, neurologic, and even psychiatric diagnoses have remained marginally effective. Preventative and predictive medicine has been stalled at the starting-gate. With meta-genomics, came the understanding that man is a super-organism, a community of thousands of species of microbes functioning in homeostasis with the human genome. Proteomics and Metabolomics have built on this foundation with the knowledge that even seemingly similar diseases result not from a single transcriptional dysfunction of DNA, but from thousands of dysfunctional interactions between the host and its micro-biome the ‘Interactome’. Antibodies are produced against components of the human micro-biome, so we all possess antibodies, even in the absence of disease. Antibody poly-specificity causes some of these to become auto-antibodies, with a definable autoimmune target. The ELI-Viscero panel, for example, measures 24 auto-antibodies which are part of a normal healthy human body, often called “natural” auto-antibodies. It appears that their proper homeostasis is essential to maintenance of a healthy body. Inflammation generated by other autoantibodies can lead, over time, to a diagnosis of chronic disease, or to an inflammatory cancer. Fortunately, the retargeting of an approved drug (Olmesartan Medoxomil) has allowed quick translation of immune-stimulative, rather than immunosuppressive therapies, resulting in a clinical paradigm shift, and improved opportunities for rapid molecular discovery.
Mandrik Mark
I.M. Sechenov First Moscow State Medical University, Russia
Title: Viral myocarditis as a model to clearly demonstrate the impact and role of the human endomicrobiota changes into the development of chronic autoimmune diseases
Biography:
Mandrik Mark is a student of I.M. Sechenov First Moscow State Medical University. He is a Member of Young Research Team under the aegis of EPMA (Brussels, EU) and ISPM (Tokyo, Japan). He is an author of serial articles about PPPM. He is also a Developer of several multimedia guides to Chemistry and Microbiology. His sphere of interests is meta-genomics, microbiology & immunology, autoimmune and chronic diseases.
Abstract:
Myocarditis is a chronic disorder with an autoimmune component which characterized by inflammation, decrease in myocardial function and damage of the heart muscle. In the case of no treatment, this process may lead to end-stage cardiac failure and death. Several thousand patients per year are diagnosed with this condition. Understanding that myocarditis is a disease of adult and pediatric patients make the situation worse. Experts believe that 5% to 20% of all cases of sudden cardiac death in children and young adults are due to myocarditis. Although inflammatory cardiomyopathy is more common among men, there is no convincing evidence of a genetic predisposition to the development of this disease. Moreover, the biomarkers, which certainly predict myocarditis development before manifestation are still unknown. Although, the exact causes of an individual case of myocarditis are not identified, it is possible to conclude that the main case of the myocarditis development is an infection while molecular mimicry is a mechanism of autoimmunity progressing and therefore development of chroniÑ disorders. Consequently, the question “Could the changes in the human endomicrobiome be an inducing factor in the myocarditis development?” is still open. The PIFAS (post-inflectional autoimmune syndrome) conception can throw light on the mechanism of viral myocarditis progressing. But only creating and clear understanding with bioinformatics instruments, full pathologic pathways maps enable to find biomarkers of novel generation, determine targets and discover high-efficient drugs based on personalized features.
Borovikov Artem
I.M. Sechenov First Moscow State Medical University, Russia
Title: Autoimmunity and autoimmune disorders-genomics and genome-based applications to set up biobanks networks and to secure genetic passportization
Biography:
Borovikov Artem is studying at I.M. Sechenov First Moscow State Medical University in the Faculty of Medicine since 2010. He is interested in human genetic and application of genomics technology in clinical use. He is also a Member of Young Professional section of EPMA and have several publications in Life Science Journals.
Abstract:
The number of people suffering from autoimmune diseases increases every year. Active growth related with two problems: Initial symptoms are often intermittent, unspecific until the condition becomes acute and a shortage of methods for the preclinical diagnostics. Discovering new biomarkers for early prediction and diagnosis is a chance for control rate and courses of autoimmune disease. The development of most autoimmune diseases includes a strong heritable component. Genetic contribution to autoimmunity is often complex interactions different genes and their products. Genomics based research can give a lot of new information about the potential risks and compounds, those can be optimal biomarkers of early prediction and indicate stage more accurately. But researchers need a lot of data to achieve real goals. Today most of the studies usually are disease-specific and limited in resources. More information-sharing and crossover among research projects on different autoimmune diseases is needed to stimulate them effectiveness. Biobanking is a primary tool for ensuring easy availability of high-quality biomaterial collections that combine essential samples and epidemiological, clinical and research data for autoimmune disease. In some cases, individual biobanks often do not have the required number of well-characterized donor materials. Possibly, the solution of this problem is networking some biobanks merging their records and evaluating them collectively. This method gives access to larger cohorts than would be possible through individual biobanks. It is opening new horizons for researchers but creating networks makes a new problem with legal, ethical and financial aspects of them work.
Irina Zhegalova
I.M. Sechenov First Moscow State Medical University, Russia
Title: Application of bioinformatics in autoimmune disorders for identifying druggable pathways and promising targets
Biography:
Irina Zhegalova is a student I.M. Sechenov First Moscow State Medical University, School of Pharmacy. She is a Member of Young Research Team under the aegis of EPMA (Brussels, EU) and ISPM (Tokyo, Japan). She is interested in bioinformatics and performs researches in application of this branch to PPPM model.
Abstract:
Targeted therapy is based on the binding of the target molecule which blocks or modifies the action of the target. The roofs of such a treatment are laid deeply in drug discovery e.g., the process by which drugs are designed or discovered. Creation of product from the original idea takes 12-15 years and costs up to $1 billion. Past records have indicated that the high failure rate (only 8% of success) of drug development can be attributed to the improper target pre-selection. So target discovery is the most crucial step in the modern drug discovery campaign. In this sense, autoimmunity is often caused by concomitant dysfunctions and imbalances at once. Due to the complicated nature of autoimmunity which is manually infeasible when examined on the proteomic level, researchers often employ machine learning methods to identify solutions. Machine learning approach allows to collect a set of samples “training data” which specify the correct output for a given input. A machine learning algorithm takes these examples and produces a program which may work with other sets perfectly. Bioinformatics provides completely new approaches which involve an artificial intelligence to target discovery process. Data mining of available biomedical data has led to a significant increase in target identification. Therefore, data mining would allow for using bioinformatics not only in identifying but also in selecting and prioritizing potential targets.
Alisa Petkevich
I.M. Sechenov First Moscow State Medical University, Russia
Title: Systemic autoimmune disorders: SLE and RA as an illustration of the clinical and predictive value of DNA-abzymes as unique biomarkers of newer generation to monitor the disorders at subclinical and clinical stages and to manage the disorders
Biography:
Alisa Petkevich has graduated from I.M. Sechenov First Moscow State Medical University and she is currently pursuing Post graduation in Experimental Oncology in N.N. Blokhin Russian Oncological Research Center; being involved into implementation of the national grants attributed to biomarkers as applicable to predictive diagnostics of the diseases.
Abstract:
Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are examples of systemic autoimmune rheumatic diseases (sARDs) which are thought to develop as a result of the autoimmunity-related control mechanisms failure where the tolerance breakage would dominate. Biomarkers to suit the clinical standards and practical requirements should fit into the concept of PPPM and evidently demonstrate their high specificity, accuracy, sensitivity and reproducibility. One of the putative and unique biomarkers of the latest generations to secure the reliable monitoring of sARDs at both clinical and subclinical stages of the disorder (either SLE or RA) are appearing to be DNA-abzymes i.e., DNA-hydrolyzing auto antibodies (auto Abs) of IgG class exhibiting catalytic activity. However, most of sARDs tested in particular SLE and RA have a typical subclinical stage preceding to the canonical clinical manifestations which in turn are usually accompanied by the presence of the disease-related biomarkers to correlate with the initiation and propagation of the autoimmune condition. Among those biomarkers, catalytic auto Abs including DNA-abzymes are initially registered in sera of the persons tested at the subclinical stage (with no clinical signs) to let us speak about DNA-abzymes as subclinical and predictive biomarkers to correlate further with symptoms of the clinical illness. The presence and levels of those DNA-abzymes in sera of SLE and RA patients with different forms of the disease and in sera of the persons-at-risk illustrating the subclinical (symptom-free) stage to be transformed further into the clinical one could facilitate manipulations to secure reliable procedures of getting the right diagnosis put in time to predict the relapse or exacerbations, to control the clinical course and thus the drug dosing process and finally to monitor the subclinical and clinical courses and to manage the drug responses and the pathology development as a whole as well.
Dmitrii Cherepahin
I.M. Sechenov First Moscow State Medical University, Russia
Title: Organ-specific autoimmune disorders: Translational biomarkers to confirm the diagnosis and to predict chronification and disabling
Biography:
Dmitrii Cherepakhin is a student of I.M. Sechenov First Moscow State Medical University. He is a Member of Young professional group in structure of EPMA. He was participant and speaker of two international congress about predictive-preventive and personalized medicine (PPPM) in Bonn and in Brussels. He is the author of serial articles about PPPM in cardio-vascular pathology and nowadays his activity leads his work in genetic and in predictive and preventive medicine.
Abstract:
Autoimmune myocarditis (AIM) usually develops in genetically predisposed individuals infected with CVB3 or related viruses to represent typical manifestations of molecular mimicry. Clinical manifestations of AIM with distinct onset vary from being asymptomatic to fatal. The biomarkers to predict the course at initial presentation have not yet been established. An improved knowledge of the mechanisms of infections to proceed with the illness should help to get type of post-inflectional autoimmune syndrome (PIFAS). PIFAS defined and then be used as a combinatorial biomarker to develop preventive strategies for quenching PIFAS at the subclinical stages. The etiology of autoimmune thyroiditis (AIT) is multifactorial and is due to the development of autoimmunity against thyroid antigens. The AITs are prototypical organ-specific autoimmune disorders but the mechanisms to trigger those autoimmune responses are not clearly known. PIFAS would be a tool to secure subclinical diagnosis of AIT and it will be new paradigm of diagnosis. Simple biomarkers that are used to assess CDIO as a multifactorial disorder are effective once the disease is well established but none, thus far is reliable for the detection of the pre-early (subclinical) manifestations. The concept of combinatorial biomarkers illustrates biomarkers to unite integral components of different but logically combined functionality. Therefore, future efforts should be focused on the validation of the combinatorial biomarkers i.e., demonstration of their close correlation to the pathological process.
Sergey Suchkov
I.M.Sechenov First Moscow State Medical University, Russia
Title: Tissue-specific autoimmune disorders: Antibody-proteases as a generation of highly informative and unique biomarkers to monitor subclinical and clinical stages of demyelination in multiple sclerosis (MS)
Biography:
Sergey Suchkov graduated from Astrakhan State Medical University and was awarded with MD. In 1985, Suchkov obtained his Ph.D. He is the PhD student of the I.M. Sechenov Moscow Medical Academy and Institute of Medical Enzymology, USSR Academy of Medical Sciences, Moscow, Russia. In 2001, Suchkov finished the PostDoc Research Fellowship Program and maintained his Doctor Degree at the National Institute of Immunology, Russia. From 1987 through 1989, Dr. Suchkov was a senior Researcher, Lab of Developmental Immunology, Koltzov Institute of Developmental Biology, USSR Academy of Sciences to deal to developmental immunology. From 1989 through 1995, Dr. Suchkov was being a Head of the Lab of Clinical Immunology and Immunobiotechnology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004, Dr. Suchkov was being a Chairman of the Department for Clinical Immunology, Moscow Clinical Research Institute (MONIKI) and the Immunologist-in-Chief of the Moscow Regional Ministry of Health. At present, Dr Sergey Suchkov, MD, PhD, is Professor in Immunology, Department of Pathology, School for Pharmacy, I.M. Sechenov First Moscow State Medical University, Dean of the Department (Faculty) of The PPPM Development, and the First Vice-President of the University of World Business, Politics and Law and Secretary General, United Cultural Convention (UCC), Cambridge, UK.
Abstract:
Most autoimmune disorders including multiple sclerosis (MS) are preceded by a symptom-free subclinical stage in which the patients can be identified by specific auto Abs. Proteolytic Abs are multivalent immunoglobulins (Igs) endowed with a capacity to proteolyze the antigenic substrate. Abs against myelin basic protein/MBP endowing with proteolytic activity (Ab-proteases) are of great value to monitor demyelination to illustrate the evolution of multiple sclerosis (MS). Anti-MBP auto Abs from MS patients and mice with EAE (SJL and C57BL/6 mice as an animal model of MS) exhibited specific proteolytic cleavage of MBP The activity of the Ab-proteases markedly differs between: (i) MS patients and healthy controls; (ii) different clinical MS courses; (iii) EDSS scales of demyelination to correlate with the disability of MS patients to predict transformation prior to changes of the clinical course. The sequence-specificity of Ab-proteases demonstrates five sites of preferential proteolysis to be located within the immunodominant regions of MBP. Those sites are located within the immunodominant regions of MBP; and two of them falling inside the sequence covering a 81-103 peptide segment and its 82-98 subsegment as well, with the highest encephalitogenic properties both to act as a specific inducer of EAE and to be attacked by the MBP-targeted Ab-proteases very often in MS patients with the most severe (pro-gradient) clinical courses. Meanwhile, sites localized within the frame of 43-68 and 146-170 subsegments whilst being less immunogenic happened to be EAE inducers very rare but were shown to be attacked by Ab-proteases very often in MS patients with moderate (remission-type) clinical courses. In moderate courses, Ab-proteases focus their proteolytic effect on low-immunogenic 43-68 и 146-170 sites but in aggressive cases (progradient courses), the proteolysis was prevailed on highly-immunogenic 81-103 and 82-98 sites. The activity of Ab-proteases was first registered at the subclinical stages 1-2 years prior to the clinical illness. About 24% of the direct MS-related relatives (probands) were seropositive for low-active Ab-proteases from which 38% of the seropositive relatives established were being monitored for 2 years whilst demonstrating a stable growth of the Ab-associated proteolytic activity. Moreover, we see also low-active Ab-proteases (to target 43-68 and 146-170 sites) in persons at MS-related risks (at subclinical stages of MS), and primary clinical and MRT manifestations observed were coincided with the activity to have its mid-level reached. And registration in the evolution of highly immunogenic Ab-proteases to attack 81-103 and 82-98 sites predominantly would illustrate either risks of transformation of subclinical stages into clinical ones, or risks of exacerbations to develop. The activity of Ab-proteases in combination with the sequence-specificity would confirm a high subclinical and predictive value of the tools as applicable for personalized monitoring protocols. Moreover, Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism. Of tremendous value are Ab-proteases directly affecting the physiologic remodeling of tissues with multilevel architectonics (for instance, myelin). By changing sequence specificity of the Ab-mediated proteolysis one may reach minimizing scales of demyelination. Further studies on targeted Ab-mediated proteolysis may provide a supplementary tool for predicting demyelination and thus the disability of the MS patients.