Mar./2009
(STRATEGIC PROPOSALS)
Understanding and Controlling Biological Process of Chronic Inflammation/CRDS-FY2008-SP-08
Executive Summary

This strategic provides a research and development strategy to create the basis of pre-emptive medicine which would be needed in an aging society. The strategic plan includes the research to unravel and control biological mechanisms in which acute inflammation turns to chronic one causing serious disease. In this strategic program, we focus on inflammation that is invoked when a living body receives harmful stimulation. We recommend two research programs to be promoted. First one is a research to reveal how inflammatory reaction which rapidly resolved in usual turns to chronic inflammation causing a new disease. The second one is a research to develop controlling mechanisms to resolve chronic inflammation. The integration of above two approaches would establish the foundation of pre-emptive medicine for inflammation-related diseases that have become a big social and medical issue in future few years. The research programs cover not only the biological hierarchy from molecules to cells but also the one from tissues to organs.

It has been widely known that inflammation is reddening or swelling with fever and pain, as well as a repair mechanism invoked by the living body against infections and tissue injuries. However, recent studies suggested that unresolved inflammation may invade the living body in an uncontrollable condition and become a factor to cause various diseases such as neurological/muscular diseases, gastrointestinal diseases, psychiatric diseases, metabolic diseases, bone/cartilage diseases, cardiovascular diseases, sensory diseases, autoimmune diseases and cancer. Even that, it is still unclear how inflammation becomes chronic, triggers a disease and what kind of physiological role it plays. In Japan, the aging society is rapidly growing, and numerous inflammation-related diseases have brought serious problems. Although anti-inflammatory drugs have been available for many years, some of them induce adverse reactions as a result of the long-term use. We need to understand deeply the biological process of inflammation which is very common physiological reaction among the diseases described above. In the World, the research programs to approach inflammation have been focused from 2005, and several strategic programs have been developed. On the other hand, Japanese government does not establish a flame work to integrate individual inflammation-related approaches, such as immunology research, to clinical applications.

This research and development strategy is based on the study of understanding and controlling inflammation in the living body system to deliver foundations for pre-emptive medicine as follows.

1. A fundamental technology which progress the development of medicine, such as detection of turning point of the inflammatory reaction from acute to chronic and visualization of the causal relationship between the occurrence of an etiology and the development of a disease in molecular, cellular, tissue, and organ levels 2. A therapeutic foundation based on the inflammatory mechanism in the living body system, which resolves inflammation without generating adverse reactions

If the above fundamental technologies are progressed to develop pre-emptive medicines, one can expect the creation of vaccines, preclinical treatment/biomarkers for inflammation-related diseases. From the perspectives to control inflammation in the focus of a disease, this research strategy may also contribute to the development of regenerative medicine.

In the strategic program “Understanding and Controlling Biological Process of Chronic Inflammation”, we recommend to progress integrative studies covers not only the molecular and cellular biology but tissue and organ physiology based on immunology, stem cells, cardiovascular system, cancer, and neurological research fields. Therefore we provide following three approaches for this research strategy.

Biological mechanisms breaking down normal controlling process of inflammation Developing process of diseases which is triggered by chronicity of inflammation. Technology development to assess the suitable understanding and controlling the biological processing of chronic inflammation.

The current strategic plan aims to develop basic biological studies to clinical trials. According to the research team organization, molecular and cellular research core groups can collaborate with clinical research or technology assessment groups. Individual research team would progress the fundamental technology to develop in vivo control system of inflammation as well as clinical and pre-clinical researches including animal models. In addition to the team project, small individual projects should be progressed in the same time or in advance to enlarge the related-research community.

In result, the investment of strategic program “Understanding and Controlling Biological Process of Chronic Inflammation” may bring us various biological basis of pre-emptive medicines for inflammation-related diseases to sufficient current and future medical demands in Japan