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The Warsaw Voice » The Polish Science Voice » November 25, 2011
The Polish Science Voice
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One-of-a-Kind Project
November 25, 2011   
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Work to launch the Centre for Preclinical Research and Technology is under way in Warsaw in what marks the largest biomedical and biotechnology project in Central and Eastern Europe to date.

The centre is being created by a consortium of 10 research centres. The aim is to conduct interdisciplinary fundamental research and to carry out research with a view to developing new methods to diagnose and treat various circulatory and nervous system diseases as well as cancer and age-related diseases.

The project’s budget is almost zl.390 million. The project is being coordinated by the Medical University of Warsaw, in partnership with two universities—the University of Warsaw and the Warsaw University of Technology—and seven research institutes of the Polish Academy of Sciences: the Nencki Institute of Experimental Biology; the Institute of Biochemistry and Biophysics; the Mossakowski Medical Research Center; the International Institute of Molecular and Cell Biology; the Institute of Fundamental Technological Research; the Institute of High Pressure Physics; and the Institute of Biocybernetics and Biomedical Engineering.

Research work will be conducted at three levels: basic research, new diagnostics methods, and new therapeutic approaches.

Upon embarking on the project, the CePT clinical teams defined the main theoretical and practical objectives of the consortium, while the experimental groups identified the possibilities for carrying these out. Subsequently concrete steps will be taken, based on in vitro studies as well as in vivo studies made with the use of animals and on the basis of clinical material.

Research in the field of functional genomics and proteomics makes it possible to obtain a wealth of information on pathological states and their physiological context. Teams dealing with modern technologies, including nanotechnology and computer science, are taking on the challenge of enhancing biomedical research by supporting basic research and developing new diagnostic tests and therapeutic approaches.

One of the most important goals—as well as strengths—of CePT is that it combines the intellectual and experimental potential of outstanding scientists with the capabilities of a cluster of laboratories fitted with top-class specialized equipment. These include physics and chemistry laboratories (University of Warsaw), biomolecular and biotechnological labs (University of Warsaw, Polish Academy of Sciences, Medical University of Warsaw), and biomedical engineering and biomaterials technology laboratories (Warsaw University of Technology, Polish Academy of Sciences). Of special importance will be preclinical research on animal models of lifestyle diseases (Polish Academy of Sciences, Medical University of Warsaw) and contact with a clinic, doctors and patients, ensured by the Medical University of Warsaw.

Bringing together various research institutions as part of a single project will make it possible to conduct research at the level of both nanoparticles, cells and organs and the whole body. The joint efforts of the communities of physicists, chemists, biologists, computer scientists, physiologists, pharmacologists, biomedical engineers and clinicians are expected to help create new quality in the research areas involved.

State-of-the-art laboratories and apparatus are needed to achieve this aim. The project also requires effective structures for cooperation with industry, both with large companies in the biotechnology sector and innovative small and medium-sized enterprises operating in the field of diagnostics, telemedicine, and nanotechnology.

The combination of the research topics to be dealt with by the members of the CePT consortium provides for a path from basic research to the practical application of its results in healthcare and in the economy as a whole.

The project’s research program is a response to the challenges posed to modern science and medicine by lifestyle diseases, and in particular cardiovascular diseases, cancer and disorders of the nervous system.

These common chronic diseases are characterized by complex causes based on the overlapping of various pathogenic mechanisms. This makes it difficult to develop effective prevention, diagnostics and treatment methods. In this situation, only concerted efforts by a large group of scientists representing various research disciplines may lead to progress in preventing and treating the diseases in question.

Individual research areas will be led by internationally renowned scientists with substantial achievements, which guarantees active collaboration with researchers at home and abroad, and—what is especially important—that young researchers will take an interest in the project as well.

The research program, which is flexible, consists of 124 project ideas. The research agenda is a kind of navigation tool that will evolve dynamically with the progress of the research and technological advances.

The Centre for Preclinical Research and Technology will focus on the following key areas:

Diseases of the nervous system

Nervous system diseases place a particularly significant burden on the healthcare budget, accounting for 35 percent of the total costs of healthcare across Europe—more than 400 billion euros annually. According to forecasts, these expenditures will grow steadily as the population ages. What’s more, diseases of the nervous system are most often chronic and in many cases the patients are affected so seriously that they require constant care. This creates additional social costs and places an emotional and financial burden on the family as well as a financial burden on the healthcare and social security systems. In recent years, neurobiological studies have made great progress in terms of new discoveries. For example, researchers have shown the existence of a small pool of neuronal precursors in the brains of adults, and especially the enormous potential of neuronal plasticity throughout life. This last phenomenon is based on the brain capabilities for adaptive functional reorganization, which takes place at the level of networks of connections between nerve cells.

Research into plasticity processes consequently offers the growing hope that scientists will finally understand some fundamental laws governing the work of the brain, and that they will use this knowledge in clinical practice. Research findings show that plastic changes, which underlie physiological processes such as learning and memorizing, can be used to stimulate the regeneration of the brain after injury. These changes also seem to be the cause of the most important brain disorders, such as mental illness, addiction and epilepsy.

Aging and neurodegenerative diseases of old age such as Alzheimer’s and Parkinson’s as well as age-associated memory disorders generate costs totaling over 65 billion euros a year in the EU as a whole. In Poland, they affect more than 350,000 people. In the case of Alzheimer’s disease, some of the changes are symptomatic and precede the occurrence of irreversible pathological changes. The aim of the research to be conducted at CePT will be to identify proteins associated with cell death, cell cycle and calcium homeostasis, as well as neuronal plasticity. Their expression or activity changes in lymphocytes and in neurons and glia in the course of aging, in Alzheimer’s disease and in Parkinson’s.

The research should lead to the identification of specific signaling pathways and proteins that may constitute prognostic and diagnostic markers in Alzheimer’s and related diseases. The research is also expected to help determine the potential therapeutic importance of anti-apoptotic drugs and cellcycle inhibitors and to identify potential new objectives of neuroprotective therapy.

Cerebral ischemia occurs in 1 in 250 people and is the third leading cause of death in developed countries and the fourth in Poland. The chance of ischemic stroke increases with age and affects about 5 percent of people aged over 65. In the EU, the costs of treating strokes are more than 20 billion euros annually. Effective methods for preventing the death of neurons brought about by an ischemic stroke will be found only if the mechanisms of stroke are studied thoroughly. Most strokes are caused by a blockage of the blood flow in the arteries of the brain by blood clots or plaque that is created locally or reaches the brain with the blood. And neurons dying as a result of delayed post-ischemic death—in a process that goes on for hours or even days—are at the center of the neuroprotective research.

Compensating therapy based, for example, on the use of either endogenous or exogenous neurotrophins as well as stem cells, is another idea to combat the disastrous consequences of a stroke.

No less important, it seems, is the use of new diagnostic methods to better understand the relationship between the occurrence of heart arrhythmias, especially paroxysmal atrial fibrillation, and ischemic stroke.

The proposed research aims to understand the mechanisms responsible for plasticity after a stroke and to detect processes that could act pro-plastically in brains affected by the aging process and damaged by stroke.

At the cell level, dynamically changing molecular processes are especially important in the transduction of the signal leading to delayed neuronal death in brain ischemia. Along with the signal for the elimination of some cells, in areas that overcome short ischemic episodes, protective mechanisms are triggered that lead to the restoration of function and survival. Strengthening these mechanisms in areas that are unable to trigger such protective mechanisms on their own, may be an effective form of therapy.

Epilepsy is another chronic disease subject to research. The costs of treating epilepsy across the EU exceed 15 billion euros. In Poland, it has been diagnosed in 300,000 people. Recent advances in understanding the pathogenesis of epilepsy show that neuronal plasticity phenomena, including specific genes and their polymorphisms, have a particularly significant contribution to the development of this disease. This gives hope for new treatments taking into account the genetic predisposition of people at risk of post-traumatic epilepsy and stroke.

Diseases of the circulatory system

Cardiovascular diseases are the primary cause of death among people worldwide and the greatest burden on health systems in all EU countries.

Disorders of neurogenic cardiovascular regulation may have a significant impact on the formation of life-threatening cardiac arrhythmias, the development of hypertension and heart failure. The incidence of coronary heart disease and hypertension, which are a common cause of heart attack and heart failure or stroke, is particularly high in older people. Patients with hypertension require treatment for life and a stroke caused by hypertension may lead todisability. Sixty percent of patients with myocardial infarction develop heart failure and require continuous treatment; they are often unable to lead an active professional life as a result of this.

This explains why the research—planned as part of CePT—on the mechanisms of the adaptation of the cardiovascular system is so important. It will focus on issues such as the role of neuropeptides in inducing cardiovascular pathological states and on abnormal reactions of the cardiovascular system to stress in heart failure, hypertension and chronic stress. Other research topics will include the impact of chronic stress and heart failure on changes in brain gene expression and the proteins of neuropeptides regulating cardiovascular function, metabolism and reactivity to stress.

The research will also cover the issue of local and neurogenic adaptation of the cardiovascular system to pathological processes induced by metabolic disorders, respiratory and gastro-intestinal disorders as well as acute and chronic stress.

The use of stem cells in treating cardiovascular diseases

Stem cells are capable of regenerating and creating new blood vessels; using this capability of stem cells can open up new prospects for Polish cardiology. Clinical trials involving stem cells in patients after myocardial infarction and heart failure haveproduced moderate success so far. It is therefore necessary to conduct further research in the in vitro ex vivo system, to better understand the biological conditions underlying angiogenesis processes.

The main subject of the laboratory’s work will be to explore the possibilities for controlling the processes of cell differentiation, angiogenesis and regeneration, with a particular emphasis on research on cell cultures.

Cancer

Cancer is currently the second biggest cause of mortality in EU countries. The number of deaths related to cancer is growing, particularly among middle-aged people.

One of the key objectives of the CePT project is to conduct research to discover new mechanisms of oncogenesis and develop new therapeutic methods. The consortium has the necessary clinical facilities in the form of Medical University of Warsaw hospitals and has great intellectual potential based on top experts in experimental and clinical oncology.

Research projects in the field of oncology will focus on the etiology of cancer and on the mechanisms of neoplastic transformation of cells. This will include research on the mechanisms of DNA damage and ways of preventing them, as well as research on the genetic instability of in vivo and in vitro cells, and cutting-edge research on the role of chaperone proteins in oncogenesis. The results of the research will make it possible to better understand the mechanisms of neoplastic transformation and to identify factors that might in the future be used in cancer prevention therapy.

Genetic cancer markers

Another group of consortium projects involves the identification of methods for rapid and inexpensive determination of genetic markers of different types of cancer as well as pharmacogenetic research related to cancer therapy. The molecular diagnostics of cancer and the determination of the pharmacogenetic profile of the patient is a modern tool for predicting the course of the disease and for selecting optimal, specific, individualized treatment methods. This opens up new prospects for treatment and can bring tangible benefits, both clinical and economic.

Signaling and metabolic pathways in cancer cells

The identification of signaling and metabolic pathways in cancer cells could be a potential goal of a specific, targeted therapy. Research in this area will focus on gliomas, leukemias and other cancers. In principle, the research is expected to lead to the identification of new cellular ontogeny pathway inhibitors, especially new protein kinase inhibitors, such as MAPK kinase cascade and tyrosine kinases. Methods will be developed for the synthesis of such potential factors, and their therapeutic efficacy will be tested in different experimental in vitro and in vivo systems (models). These studies create opportunities for obtaining completely new compounds with better therapeutic efficacy.

Prevention and anticancer therapy

Research is also planned at CePT on the possibilities for using various compounds of natural origin, such as flavonoids, in both preventing and treating cancers, as well as research on improving other modern treatment methods such as photodynamic therapy.
Another important issue, both scientifically and clinically, is the potential impact of nanoparticles on the formation of tumors.

New technology

Modern biomedicine is developing at a rapid pace, largely due to technological progress in many areas. Very often, research on new treatment methods must be interdisciplinary in nature in order to be successful. The joint work of the research teams from the Polish Academy of Sciences and the universities covered by the CePT program in fields including technical, chemical, physical, mathematical and computational, biological and medical sciences, is hoped to make it possible to exceed a critical mass. This creates a significant added value in the work conducted, oriented at taking up significant challenges such as those involving the most serious lifestyle diseases. The consortium will work to upgrade diagnostic techniques and develop new ones. Projects in the area of nanomedicine, for example, are aimed at bringing radical innovation to medical diagnostics through the use of the achievements of nanotechnology. Examples include the use of nanoparticles for labeling tissues, proteins and cells and the use of imaging devices with nanometer resolution to examine the structure of cells and biomolecules. This is expected to result in the development of fast and ultra-sensitive in vitro diagnostics techniques, for example in “lab-on-a-chip” projects, in addition to microfluidic and lithographic techniques.

The possibility of enhanced cooperation between the UW, PW and PAN teams on the one hand and the medical community on the other offers a hope for more effective research on diagnostic methods. As part of the consortium, conditions will be created for testing diagnostic methods in areas identified by the Medical University of Warsaw, according to the needs of patients. Opportunities will be created for the development of technology along the value added chain, from phenomena at the molecular level, on a scale of 1 nm, to the prototypes of new equipment and diagnostic protocols. This is expected to lead to a reduction in the costs of diagnosing lifestyle diseases and finding out key facts about their causes.

Diagnostic technologies, including in vitro methods, are relatively quickly put to commercial use, not only by large corporations, but also by small and medium-sized companies. The development of medical diagnostics as part of the CePT consortium will create conditions for attracting investors interested in setting up firms and creating jobs in the area of medical diagnostics.

Telemedicine applications, particularly in cardiology, are another important area for the development of medical diagnostics. WUM research teams are an invaluable partner for Polish SMEs developing innovative miniaturized sensors and algorithms in processing digital signals, including the ECG signal. The application of telemetry in the form of smart remote diagnostic and cardiological monitoring systems will make it possible to enhance the effectiveness of prevention and therapy for patients with heart failure and heart rhythm disorders (in Poland, this group numbers more than 2 million patients in all). The same goes for neurological patients, particularly those in a risk group and those who have had incidents of stroke.

Drugs of the future
One of the strategies developed by the CePT consortium involves a search for new drugs. Biologically active chemical compounds would be used as non-biological synthetic drugs in treating neurodegenerative diseases, cancer, diabetes, diseases caused by thedefective functioning of the mitochondria, as well as various forms of addiction, pain, learning and memory disorders, and cardiovascular diseases. The development of new methods for pharmacological intervention should be made easier by an increasingly better insight into the pathomechanisms and molecular basis of these disorders. More advanced methods of combinatorial chemistry and computer assisted drug design make it possible to design molecules endowed with optimal structural parameters. In addition to the increased therapeutic efficacy of selected synthetic drugs, these preparations will have a significant economic advantage over drugs currently available on the market. The cost of synthesizing a small, biologically active particle is much lower than the cost of producing biological drugs.

The CePT partners do not limit themselves to conducting research on their own, but often work with innovative pharmaceutical companies at the stage of research and preclinical testing. These projects include long-term cooperation with foreign companies (such as Wista Laboratories) in the treatment of neurodegenerative diseases, and collaboration with domestic firms (such as Adamed) in the area of cardiovascular diseases and type 2 diabetes. As a result of the CePT project, this area of cooperation with industry will intensify substantially thanks to the creation of modern high-standard laboratories and the purchase of high-end research equipment.

Another type of research into new treatment methods will be based on the knowledge of genomics and molecular biology. Increasingly effective DNA analysis methods enable comprehensive molecular diagnostics and assessment of the risk of disease. These methods will be used to define new genetic markers revealing predisposition to diabetes, cancer and neurodegenerative disorders. An insight into the genetic mechanisms behind the development of these diseases will be of enormous therapeutic importance.

A separate, but methodologically related issue is the use of genetic analysis in pharmacogenomics. One of the objectives in this area of research is to identify genetic factors that determine both the side effects of drugs and the lack of a therapeutic effect. Analysis of the impact of genetic polymorphism on the metabolism of drugs will make it possible to develop more effective, individualized treatments for neurodegenerative diseases, cancer and ischemic disease as well as other lifestyle diseases—such as affective disorders of the central nervous system, obesity, metabolic syndrome, diabetes, atherosclerosis, hypertension and osteoporosis—which are a key factor in reducing the quality of life and life expectancy. Distinguishing between patients with varying sensitivity to the drug will, in turn, make it possible to avoid unnecessary costs and the harmful effects of prolonged treatment.
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