In rare disorders the process of translation from laboratory observation to effective drugs require particular expertises. Besides a thorough understanding of human pharmacology, investigators will need to be trained in use of preclinical model systems, the development of quantitative indices of drug mechanism and response, the use and interpretation of genomic, lipidomic and proteomic information, the physiology of evoked phenotypes, novel biomarkers, and the use of bioinformatics to harvest and integrate preclinical and clinical information relevant to drug response. In this application we propose a new educational experience to integrate elements of disciplines previously segregated within basic science and clinical medicine. The translational space imposed on the process of drug development is defined as stretching from Proof of Concept (PoC) in cells and model systems to completion of studies of drug mechanism and variability of response that afford a basis for individualized dose selection. An effective translation from bench to bedside requires not only a close networking between basic scientists and clinicians but also the need to address ethical and regulatory issues. These last include pre-clinical and early-phase clinical development, biomarker validation, study design and management, data analysis, regulatory submission and research governance.

It has recently been discovered that the innate immune system can recognize key molecular signatures borne by pathogens called pathogen-associated molecular patterns (PAMPs). Receptors that recognize these PAMPs, referred to as pathogen-recognition receptors (PRRs), play a key role in eliciting inflammation. More recently it has been shown that damage associated molecular pattern molecules (DAMPs) present on molecules released during cell damage can also be recognized by macrophages and other cells of the immune system. There is now a large and growing body of evidence that DAMPs recruit inflammatory cells and mediate signals between lymphocytes, dendritic cells and macrophages. The study of PAMP- and DAMP-mediated innate immunity activation represents a new and very promising frontier in research related to the pathogenesis of chronic inflammation. The recognition of the role that PAMPs, DAMPs and their receptors play in inflammation could lead to the identification of drugs that can selectively target and/or modulate the activity of the innate immune system.
Go to event II

Many rheumatic disorders, such as rheumatoid arthritis, are considered secondary to an abnormal, Th1 skewed, response. Others, such as systemic lupus erythematosus, are characterized by an abnormal B cell response. Recently, however, strong evidence has emerged pointing to an important role of B cells also in the pathogenesis of other diseases, such as rheumatoid arthritis. Finally, a major advance in recent years has been the identification of physiological regulatory mechanisms within the cellular immune response. Several types of regulatory T cells suppressing the function of other T cells have been identified, and there is growing evidence of the role that these mechanisms play in the pathogenesis of autoimmune diseases. In particular, in juvenile idiopathic arthritis there is evidence that endogenous heat shock proteins may elicit specific regulatory T cells. Moreover, mesenchymal stem cells have been shown to be able to exert important immunomodulatory effects. All these finding open new avenues of therapeutic possibilities that can exploit the physiologic regulatory mechanisms that operate within the immune system.

Over the last decade biological therapies have represented a major advancement in the treatment of rheumatic diseases. Despite this progress, however, several problems remain. At the same time, breakthroughs in basic and applied research are yielding a myriad of new potential targets for therapies.

The final conference in the TRiPR series of events - Biological Agents and Emerging Treatments in the Management of Rheumatic Diseases - will address the treatment of both adult and childhood rheumatic diseases with the purpose of reviewing and discussing the progress that has been achieved thus far, the unmet needs that are still faced, and the potential new treatments that the future holds in store. A final session will be devoted to strategies to improve methodologies of translational research on and clinical development in common, as well as rare, forms of rheumatic disorders.