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Agency: Cordis | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2014 | Award Amount: 144.00K | Year: 2015

We are proposing a four-year programme of knowledge transfer and networking between Aston University (ASTON, UK), Universitatsklinikum Erlangen (UKER, Germany) and Redoxis AB (Redoxis, Sweden). Our proposal targets an emerging area of biology, i.e. reactive oxygen species (ROS)-mediated regulation of immune responses; it brings together the application of small molecule candidate drugs to generate ROS, with use of innovative approaches to biomarker identification in models of chronic inflammatory disease. This research has significant potential for application in human health and is of particular relevance to the ageing population. Research training, innovation and knowledge exchange for early career researchers, achieved by combining our cutting edge expertise, is important to extend the EUs reach in this emergent area. Interchange in this way will facilitate and promote our early career researchers to develop into tomorrows research leaders of redox biology in chronic inflammation. It will encourage new, cross-European collaboration between academia and industry ensuring that we maintain our leading position world-wide. This tri-partite consortium brings together groups with highly complementary expertise to exchange knowledge and develop staff: ASTON in the biochemical analyses of ROS, the effects of immune cell thiol oxidation in vitro and ex vivo and biomarker identification; UKER - in animal models of chronic diseases such as rheumatoid arthritis; and Redoxis - in development of novel drugs that stimulate production of ROS from the NOX2 enzyme as means to modulate chronic inflammation. The project objectives and challenges present a balanced mix between industrial application and basic science, which is focused on knowledge transfer and drug development. Through future collaborative funding, we anticipate far-reaching applications of redox modulators to manage chronic disease and increases in knowledge of both autoimmunity and ageing of the immune system.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2011.2.2.1-2 | Award Amount: 17.04M | Year: 2012

NEURINOX aims at elucidating the role of NADPH oxidases (NOX) in neuroinflammation and its progression to neurodegenerative diseases (ND), as well as evaluating the potential of novel ND therapeutics approaches targeting NOX activity. NOX generate reactive oxygen species (ROS) and have emerged as regulators of neuroinflammation. Their role is complex: ROS generated by NOX lead to tissue damage in microglia-mediated neuroinflammation, as seen in amyotrophic lateral sclerosis (ALS), while absence of ROS generation enhances the severity of autoimmune-mediated neuroinflammation, as seen for e.g. in multiple sclerosis (MS). The objective of the 5 years NEURINOX project is to understand how NOX controls neuroinflammation, identify novel molecular pathways and oxidative biomarkers involved in NOX-dependent neuroinflammation, and develop specific therapies based on NOX modulation. The scientific approach will be to: (i) identify NOX-dependent molecular mechanisms using dedicated ND animal models (ii) develop therapeutic small molecules either inhibiting or activating NOX and test their effects in animal models (iii) test the validity of identified molecular pathways in clinical studies in ALS and MS patients. NEURINOX will contribute to better understand brain dysfunction, and more particularly the link between neuroinflammation and ND and to identify new therapeutic targets for ND. A successful demonstration of the benefits of NOX modulating drugs in ALS and MS animal models, and in ALS early clinical trials will validate a novel high potential therapeutics target for ALS and also many types of ND. NEURINOX has hence a strong potential for more efficient ND healthcare for patients and thus for reducing ND healthcare costs. This multi-disciplinary consortium includes leading scientists in NOX research, ROS biology, drug development SMEs, experts in the neuroinflammatory aspects of ND, genomics and proteomics, and clinicians able to translate the basic science to the patient.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.4.5-12 | Award Amount: 14.81M | Year: 2008

Objective: To delineate the biological and molecular pathways that initiate and drive chronic inflammatory disease and to transform the knowledge obtained into the development of novel anti-inflammatory interventions. Focus will be given to Rheumatoid Arthritis (RA) since longitudinal data indicate that intensive treatment can prevent persistency and chronicity. State of the Art and beyond: The first generation of targeted therapies in chronic inflammatory disease used RA as prototype disease for clinical development. These therapies are now also used in other inflammatory disorders. Although treatments have been developed that are effective in a proportion of patients, they are aspecific, relatively toxic and do not mediate cure. Currently, it is unknown which molecular effects need to be induced and/or targeted to prevent induction or persistency of RA. However, this is within reach through a strong international consortium of world-leading European groups that cover both basic- and translational research. Work plan: The general strategy for the project is to enable parallel studies that are focussed on critical switch moments in the biological processes that drive chronicity of inflammation. As the consortium consists of a multidisciplinary team with basic- and clinical expertise, translational research will be conducted to delineate the molecular basis of dysregulated inflammation, the RA-specific autoimmune-response and organ specific pathobiology. The final aim is to develop novel- and specific anti-inflammatory therapies. Impact of the project: This project will (i) identify the molecular networks underlying chronic inflammation and thereby (ii) will define novel targets for drug-development as well as (iii) algorithms that will predict outcome of therapy. Moreover, within this project European SMEs will evaluate new interventions (iv) and this project will (v) offer a platform to rapidly develop ideas and patents into new therapies.

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