RICERCA ITALIANA     

Center of Excellence on Aging

Università degli Studi "G. d'Annunzio" Chieti-Pescara

Abstract

By 2010, more than one in five Italians will be 65 years or older. We intend to establish a Center of Excellence on Aging (CEA) with the aim of focusing multidisciplinary research efforts at our Institution on the aging process. Three main areas will be targeted at CEA: cardiovascular disease, cancer and neurodegenerative disorders. Within each area, there is clearly a need for early diagnosis thus allowing a tolerable and successful treatment, as well as a need for a better mechanistic understanding leading to the development of novel treatment paradigms. We plan to pursue both objectives by integrating basic and clinical research into a 13.500 m2 dedicated research building (CE.SI). In the cardiovascular area, we will study age-related mechanisms amplifying the effects of other risk factors (eg hypercholesterolemia, hypertension and diabetes mellitus) on the determinants of atherothrombosis and its complications. In the cancer field, we will study the molecular mechanisms controlling cell proliferation, aging and apoptosis in cancer cells. Moreover, we will explore the potential of non-specific and specific immunity to block the progression of mammary, prostatic, colonic and pleuro-pulmonary carcinogenesis. The expertise developed in the cardiovascular field will also be exploited to investigate the role of platelet activation, oxidant stress and chronic inflammation in Alzheimer's disease. Novel experimental models (including stem cell expansion and transplant), molecular epidemiology and molecular markers of disease will be developed jointly across these areas.

There is also a need for improving the utilization as well as the benefit/risk ratio of existing preventive/treatment strategies in the elderly. We intend to pursue both aims by promoting patient-oriented-research (POR) at our Institution, through a newly established Clinical Research Center (CRC) within CE.SI interconnected with the existing Institute of Advanced Biomedical Technology (ITAB). The sophisticated neuroimaging techniques developed by ITAB will allow the implementation of novel diagnostic paradigms in neurodegenerative disorders. Moreover, the availability of a CRC dedicated to phase I/II studies in elderly patients will allow an early assessment of novel treatment strategies as well as a reappraisal of the pharmacokinetics and pharmacodynamics of existing drugs with the aim of optimising their benefit/risk profile in the elderly.

CEA intends to foster post-graduate training in the above areas, both at the basic science level (through a Ph.D. programme on Aging) and in clinical research through a POR course and a Master in "Aging and Quality of Life".

CEA is developing a research partnership with major pharmaceutical companies (eg Merck & Co., Bayer AG, Novartis, Roche) on selected projects in the three main areas. The Principal Investigators on this grant proposal have already established solid collaborations with national and international research institutions that will ensure a training network for young Investigators working at CEA. The Scientific Coordinator of CEA will be assisted by an International Advisory Board in assessing the overall programme and reviewing progress toward the stated objectives.

CE.SI is an established research center with its own faculty and facilities. Therefore, the financial support from MURST will be allocated primarily to aging-related research and educational activities, short-term recruitment of young investigators, medical, nursing and technical personnel working in CEA core facilities. This strategy is aimed at the education and professional training of scientists and health care workers with a commitment to the diseased elderly, beside ensuring continued activity of CEA beyond the funding period. <<<

Principal Investigator

Carlo PATRONO Università degli Studi "G. d'Annunzio" CHIETI-PESCARA

International Relationship

Investigators working at the Center of Excellence on Aging (CEA) have scientific collaborations with major Research Institutions including: Consorzio "Mario Negri" Sud, Catholic University of Rome, Univ of Bologna, Milan, Perugia, Rome and Torino, National Institute of Health (Rome), European Institute of Oncology (Milan), National Cancer Institute (Milan), IRCS "C. Besta" (Milan), University of Pennsylvania (Drs. G.A. FitzGerald, F. Catella-Lawson, Dr. C. Funk), University of Utah (Dr. S.M. Prescott), INSERM U-348, Paris (Dr. A. Habib), University Hospital Rotterdam (Prof. P.J. Koudstaal), Columbia University (Dr. A.M. Schmidt), University of Saarland, Germany (Dr. U. Sahin), Genetic Institute, Andover, MA (Dr. S. Wolf), Human Genome Sciences, Rockville, MD (Dr. S. Giri), National Cancer Institute, NIH, Bethesda, MD ( Dr. Robert Callahan), University of Maryland at Baltimore, MD (Dr. R.C. Gallo), VA Medical Center Boise ID, (Dr. R.D. Olson), INSERM "La Salpetrière" Paris (Prof. Y. Agid), Neurology Institute, National Hospital London (Prof. A. Lees, Dr. C. Bathia), The Mount Sinai School of Medicine (Prof. W. Olanow), NIH Bethesda (Prof. M Hallett, Prof. J. Guralnick), Neurology Institute National Hospital London (Prof. Scaravilli), Department of Neuroimmunology Vienna (Prof. H. Lassmann), NY Medical College, Valhalla NY (Dr. N.G. Abraham, Prof. J. McGiff), University of Texas Health Science Center at San Antonio, TX (Dr. R. De Fronzo), Brigham and Women's Hospital, Harvard Medical School, Boston (Drs. J.K. Liao, P. Libby, C. Serhan), Central Institute of Biomedical Engineering University of Ulm (Prof. S.N. Ernè). These collaborations will be further developed: a) to pursue specific research projects; b) to ensure a training network for young Investigators working at CEA; c) to recruit promising Investigators from these Institutions at the Assistant Professor level.

A number of Italian subsidiaries of multinational pharmaceutical companies (including Bayer, Bristol-Myers-Squibb, Eli-Lilly, Merck Sharp & Dohme, Pharmacia & Upjohn, Pfizer, Roche, Searle-Monsanto and Sanofi-Synthelabo) are currently supporting specific research projects of the participating Investigators and are willing to support training programs in Patient-Oriented-Research at CEA. It is expected that this will have important financial and social returns to these companies through a considerable growth of presently limited phase I/II studies in Italy (the General Clinical Research Center at CEA as a model for other Institutions) and therefore increased medical recruitment by these companies.

Moreover, CEA has received letters of intent from the following multinational companies' headquarters for direct funding of specific research projects to be developed at CEA during the period 2001-2003: Bayer AG (Novel approaches to antioxidant treatment in diabetes mellitus), Merck & Co. (selective inhibitors of COX-2), Novartis (atypical antipsicotic drugs), Pfizer (long-term ICE in Alzheimer's disease) and Roche (advanced and fluctuating Parkinson's disease). <<<

Research Objectives

The strategic objective of the Center of Excellence on Aging (CEA) is to promote multidisciplinary research within the University of Chieti (in collaboration with a research network and industrial partners, as detailed at 2.4) in three main therapeutic areas: cardiovascular disease, cancer and neurodegenerative disorders. Each area will be targeted with aging-related research projects, by integrating basic and clinical research into a 13.500 m2 dedicated research building (CE.SI) built with a $28.5 million grant to MURST for the University of Chieti through law 64. CE.SI has 4.400 m2 of basic research labs, 4.400 m2 of clinical research space including a General Clinical Research Center (GCRC) with 30 beds and 4.700 m2 of centralized facilities and administrative offices. CE.SI is endowed with approx $11 million worth of state-of-the-art instruments and special equipment, including core facilities [eg gas chromatography/ mass spectrometry (GC/MS) lab]. CE.SI is interfaced with the Institute of Advanced Biomedical Technology (ITAB) and with the University Hospital within the same Campus. ITAB is a 5.000 m2 core facility cofunded by the University of Chieti and the European Union and devoted to basic and clinical research on imaging. Research space within CE.SI has been allocated on a competitive basis to basic and clinical Research Groups working or recently recruited to the University of Chieti, with the aim of focusing multidisciplinary research efforts on the aging process. Research labs without departmental boundaries will allow cross-fertilization of research ideas and methodologies from different disciplines, and will allow cost-containment through space- and time-sharing of costly facilities. Co-localization of basic and clinical research in one dedicated building will allow synergistic interactions between the two, with the ultimate goal of developing and testing research-based diagnostic and treatment paradigms for the elderly. <<<