Deutsches Rheuma Forschungszentrum Berlin

Berlin, Germany

Deutsches Rheuma Forschungszentrum Berlin

Berlin, Germany

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Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.4.2-3 | Award Amount: 3.92M | Year: 2011

Until the age of biotechnology, treatment options for children and adolescents with severe arthritis, inflammatory bowel diseases and other serious diseases with chronic inflammation were limited. Advances in understanding the pathophysiology of the inflammatory responses have led to the development of a new class of medications that are capable of inhibiting selectively the principal mediators of inflammation and tissue damage. The introduction of these new immunomodulators, which are collectively termed biologics, has opened a new era in the treatment of inflammatory diseases. Recent reports however suggest unexpected increases in adverse - or serious events -associated with the use of these biologics. PHARMACHILD aims to detect, assess and understand long term and short term side effects of the use of biologics by studying the pharmacovigilance in a large international cohort of patients with Juvenile Idiopathic Arthritis (children and young adults) in order to support regulatory decisions on marketing authorizations for these products. There is a clear need for a study that will enable the promotion of more effective and safer use of biologics in JIA as children and young adolescents represent an especially vulnerable patient group, JIA is the most common chronic disease of childhood treated with biologics, and data available from adults cannot be extrapolated to children. PHARMACHILD brings together leading European scientists in the field of infectious diseases, immunity, inflammation and oncology. Our network combines resources from international organizations and existing national registries. This combination will enable us to achieve the critical mass (in terms of expertise and resources) to identify the risk factors for developing adverse events, to elucidate the mechanisms involved in the adverse events (such as latent infection reactivation) and to develop methodologies for screening and predicting patients at risk.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.23M | Year: 2012

Inflammatory rheumatic diseases affect millions of European citizens causing chronic pain, disability and premature death. Curative treatments are lacking. Conventional research often focuses on one single organ system such as the bone or the immune system and. ignores interactions between organ systems. OSTEOIMMUNE is a supra-disciplinary training network that targets this gap by providing comprehensive, structured and coherent training. The scientific training within OSTEOIMMUNE reflects the participants common research programme aiming to unravel the interactions between the immune system and the skeleton. A group of outstanding European scientists in genetics, (osteo-) immunology, rheumatology and drug development has joined to form OSTEOIMMUNE to provide 12 ESRs and 2 ERs with training in a broad range of laboratory and complementary skills and capacities. OSTEOIMMUNE participants represent 7 of Europes most active academic centres in arthritis research and 3 highly innovative biotech and pharmaceutical companies. All have contributed important concepts to the field, five groups have earned the title Centre of excellence. OSTEOIMMUNE participants have an outstanding history of successful collaboration which is reflected in numerous influential joint papers and common efforts in national and European networks (e.g. DFG: IMMUNOBONE, BMBF: IMMUNOPAIN, FP6: EURO-RA, AUTO-CURE, FP7: MASTER-SWITCH) and have trained numerous highly successful ESRs and ERs. Our young investigators will leave the network after successful completion of their training with a set of aptitudes that will enable them to be instrumental in developing curative therapies towards rheumatic diseases, be it in an academic, clinical or industrial setting. Moreover, OSTEOIMMUNE will establish a long-lasting consortium for cutting edge research in the field of osteoimmunology, leading to accelerated and integrated discoveries, which can become commercially exploitable first by European industry.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.76M | Year: 2012

Immune-mediated inflammatory diseases (IMID) are important health challenges in Europe and beyond, afflicting an estimated 5-8% of the total population. IMID with an onset during childhood such as Juvenile Idiopathic Arthritis (JIA) cause particular concern as pediatric patients form an especially vulnerable group. Currently there is no safe and cost-effective cure for JIA and related juvenile IMID. Thus, these children face lifelong treatment with serious consequences both for the patient (high risks of long-term side effects) and for society as a whole (high costs). Translating the progress in molecular medicine into new therapies for JIA has also met with limited success. The route from idea to drug has many hurdles and is a very fragmented process. Translational medicine encompasses the continuum of activities that extend from the conception of an idea to advanced clinical testing and, ultimately, to the development of a new medical technology or drug. This itinerary includes many components that require very different skills such as biomedical research skills, design of pre-clinical and clinical trials, regulatory issues, legal issues, intellectual property rights, communicational skills and more. Such skills are often compartmentalized within three separate domainsacademia, government and industry. Each of these domains has its own set of challenges. If we are to really change the way in which we are thinking and working in the drug development process it will be essential that we start with changing the education process of our students. EUTRAIN brings together leading scientists and institutes in the field of IMID. Its goal is to provide the next generation of researchers with insights, tools and knowledge necessary to bridge the gap between bench and bedside in IMID. In doing this EUTRAIN addresses two specific needs: the need for novel therapeutic approaches for IMID and the need for novel approaches in translational medicine.


Grant
Agency: European Commission | Branch: FP7 | Program: ERC-AG | Phase: ERC-AG-LS6 | Award Amount: 2.46M | Year: 2011

Immunological memory provides immunity against recurrent pathogens, but also can induce and regulate immunopathology. In chronic immune-mediated diseases, a pathogenic immunological memory probably is the essential driver of inflammation, refractory to physiological regulation and state-of-the-art therapeutic immunosuppression, and thus a challenge for the development of novel, curative therapeutic strategies. Despite its relevance, immunological memory is poorly understood. We recently discovered memory plasma cells and professional memory T helper cells, and their organisation by bone marrow stroma and the stroma of inflamed tissues. We have identified genes and regulating function and persistence of memory and effector cells in the resting state and in chronic immune reactions. Based on these intriguing, paradigm-breaking initial results, I propose to develop and lead a research program addressing the organisation and role of immunological memory in protective immunity and in immune-mediated diseases, on the systemic, cellular and molecular level. In particular, I propose to (1) analyse the homing of plasmablasts and T helper memory cell precursors to dedicated survival niches of the bone marrow or inflamed tissues, (2) identify the niches of CD8 memory cells and memory B cells, (3) analyse the cellular and molecular composition of memory niches, (4) decipher the molecular communication between stromal cells and immune memory cells, (5) analyse how memory/effector T helper cells are reactivated, (6) define the role of memory-phenotype T cells in the periphery, (7) analyse the role of twist1 and hop for persistence and function of pathogenic Th memory/effector cells, and (8) develop strategies to selectively delete pathogenic immune memory cells.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IEF | Phase: FP7-PEOPLE-2012-IEF | Award Amount: 168.79K | Year: 2013

More than 5 million people in Europe live with inflammatory bowel disease (IBD) or rheumatoid arthritis (RA). Both diseases are characterized by chronic inflammation partially mediated by inappropriate T cell response. Effector T-cell responses can be modulated by competing positive or negative costimulatory signals, and dysregulated balance between these signals may lead to chronic autoimmune inflammation. In mice, within the CD4\ T cell population, the expression of NKG2D is primarily associated with pathological conditions and the administration of blocking anti-NKG2D antibodies ameliorated the disease in mouse models of arthritis and IBD. Therefore the aim of my project proposal is to clarify the role of NKG2D receptor signalling in CD4\ T cell biology and in the pathogenesis of autoimmune diseases. My work will implement mouse models to study the specific impact of NKG2D expressed on CD4\ T cells in the priming, formation and maintainance of memory of CD4\ T cells and their cytokine profile during homeostasis as well as in preclinical models of IBD and RA. Moreover, by global analysis of human NKG2D\ CD4\ T cells from the sites of inflammation, we aim to better understand the possible role of NKG2D in driving inflammatory responses in IBD and RA patients. By combining these approaches, we intend to get further insights into the role of NKG2D in the regulation of autoimmune diseases and to identify strategies to possibly ameliorate tissue damage and dampen inflammation.


Patent
Deutsches Rheuma Forschungszentrum Berlin and RAS Engelhardt Institute of Molecular Biology | Date: 2013-10-28

The invention relates to isolated bispecific affinity reagents, such as antibodies or antibody fragments that bind TNF and a marker molecule for macrophages and/or neutrophils. The affinity reagents of the invention enable pathogenic sub-populations of TNF to be neutralised, whilst protective sub-populations of TNF are not affected.


Patent
Deutsches Rheuma Forschungszentrum Berlin | Date: 2014-02-26

The invention relates to an interleukin-27 (IL-27) modulator for the treatment of a pathological immune response associated with acute lung disease. The invention therefore relates to IL-27 agonists, preferably IL-27 protein, for the treatment of immunopathology and/or uncontrolled inflammatory lung disease, as well as IL-27 antagonists for the treatment of immune response depression. The IL-27 agonist is preferably administered at a defined, preferably delayed, stage of infection or inflammation.


Patent
Deutsches Rheuma Forschungszentrum Berlin | Date: 2012-06-20

The present invention relates to a method for the depletion of plasma cells by depletion and/or functional inhibition of eosinophils. Another aspect of the present invention relates to an anti-eosinophil agent for use as a medicament for the depletion of plasma cells, preferably by induction of apoptosis. The invention also relates to a method for the treatment of an unwanted immune response, preferably an unwanted humoral immune response dependent on the numbers and/or activity of plasma cells, such as allergic reactions, autoimmune diseases and rejection of organs and/or tissue after transplantation, by administration of an anti-eosinophil agent according to the present invention, characterized in that plasma cells are depleted in the subject. A further aspect of the invention relates to a pharmaceutical composition comprising an anti-eosinophil agent according to the present invention, comprising preferably antibodies directed against Siglec-8 and/or IL-5, more preferably a combination of multiple antibodies directed against Siglec-8 and IL-5, with a pharmaceutically acceptable carrier.


Patent
Deutsches Rheuma Forschungszentrum Berlin | Date: 2013-11-06

The invention relates to the field of transgenic mammals, methods for investigating T-cell therapeutic function and screening active substances useful in the treatment of immune diseases, preferably autoimmune diseases. The invention relates to a transgenic non-human mammal comprising a transgenic expression construct coding for a MOG-binding T-cell receptor (TCR) chain, a T-cell receptor (TCR) protein or nucleic acid that encodes said TCR that is isolated from said transgenic non-human mammal and a method for screening one or more factors for involvement in T-cell therapeutic function in an immune disease.


Patent
TU Berlin and Deutsches Rheuma Forschungszentrum Berlin | Date: 2012-03-12

A flow cytometer disinfection module is useful for disinfecting a sheath fluid in a flow cytometer. The module includes a flow cell and at least one UV-C and/or UV-B light source. The UV-C and/or UV-B light source is disposed about the cell and irradiates a sheath fluid passing through the cell

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