Complications related to infectious diseases have significantly reduced, particularly in the developed countries, due to the availability and use of broad-range antibiotics and wide variety of antimicrobial agents. Excessive use of antibiotics and antimicrobial agents increased significantly the number of multi-drug resistant (MDR) bacteria. This has resulted in a serious threat to public health. The inexorable rise in the incidence of antibiotic resistance in bacterial pathogens, coupled with the low rate of emergence of new clinically useful antibiotics, has refocused attention on finding alternatives to overcome antimicrobial resistance. Novel strategies aiming to reduce the amount of antibiotics, but able to prevent and treat animal and human infections should be investigated, evidenced and approved. Among the various approaches, the use of graphene and its derivatives is currently considered a highly promising strategy to overcome microbial drug resistance. In line with this interest in graphene by the European Commission through the graphene ‘flagship’ initiatives, we respond in this consortium by exploring the utility of novel graphene based nanocomposites for the management and better understanding of microbial infections. The anti-microbical potential of the novel graphene based nanomaterials, the possibility of using such structures for the development of non-invase therapies together with the understanding of the mechanism of action will be the main focal points of the proposed project entitled “PANG”, relating to Pathogen and Graphene. We have gathered the essential elements, namely different academic institutions in Europe (France, Germany, and Sweden) and their associated countries (Ukraine) as well as two European companies (Graphenea-Spain and LSO Medical-France) and one company (RS RESEARCH) in one of the associated countries (Turkey). The proposed multidisciplinary project uniquely suits high-level interdisciplinary and cross-border training.

Fibrostenosis is the driving reason for the persistent need in bowel resections in inflammatory bowel diseases (IBD). Current IBD therapies are limited to solely targeting inflammation. While these therapies in some, but not all, cases lead to symptomatic disease remission, recurrent flares interspaced with periods of remission will still result in cumulative gut wall remodeling and fibrosis. Indeed, despite these therapeutic strategies to control inflammation, fibrostenosis incidence and bowel surgical resection is not declining in IBD patients, as no anti-fibrotic drugs are currently available. The aim of this project is to validate fibroblast therapeutic targets for preventing and/or treating fibrosis in IBD-patient-samples with an emphasis on C3 and/or Tyk2/STAT3 and/or NLRP3 in the evolution of intestinal fibrosis. The anti-fibrotic efficacy and mode of action of these novel immunotherapies will be studied preclinically in IBD-patient derived samples and validated in animal models of chronic colitis. In parallel, we aim to develop and validate a clinical diagnostic and prognostic pathway for fibrosis in IBD patients based on the use of non-invasive cross-sectional imaging techniques such as magnetic resonance enterography with elastography and optoacoustic. These results together will allow to design a first-in-human proof of concept randomized trial of immunotherapeutic drugs targeting complement C3 and/or Tyk2/STAT3 and/or NLRP3 pathways in intestinal fibrostenosis. Our aim is to obtain patients and regulatory approval for implementation of these novel non-invasive imaging modalities as diagnostic and prognostic tools for fibrotic IBD to allow vital future therapeutic development for intestinal fibrosis. By providing better molecular and clinical stratification of IBD patients at risk for fibrosis and by identifying and validating novel targets for anti-fibrotic therapy, we aim to pave the way in preventing and treating this invalidating IBD comorbidity.

The PREFER project will deliver an overview and evaluation of preference elicitation methods to be applied in the entire drug life cycle, i.e. in the early stages of identifying medical needs, in clinical testing, to guide decisions on reimbursement and to make decisions on withdrawal of drugs from the market. A broad array of (combinations of) patient preference methods will be tested prospectively in a large number of case studies. The availability of large patient cohorts will enable to test new methods or deviations from existing methods in a randomized manner, by comparing well-known methods with newer ones. The use of simulation studies will both contribute to smarter design of case studies and to exploring the sensitivity of outcomes of preference studies. Based on discussions with a broad representation of stakeholders e.g. patients, patient organisations, regulatory authorities, HTA bodies and reimbursement agencies, suitable methods will be tested and their contributions to improved decision making will be discussed in recommendations adapted to the needs of all relevant stakeholders. The recommendations from PREFER are expected to lead to changed practices, in that industry will routinely assess whether a preference study would add value at key decision points in the medicinal product life cycle and, if so, implement patient-preference elicitation studies according to the PREFER project recommendations. The PREFER consortium consist of 16 industry partners and 16 academic and SME members including representation from academia, patient organizations, HTA bodies, reimbursement agencies, and project management.

We are proposing a four-year programme of knowledge transfer and networking between University of Surrey (SURREY, UK), Aston University (ASTON, UK), Friedrich-Alexander Universitat (UKER, Germany) and Redoxis AB (Redoxis, Sweden). The project targets an emerging area of biology, i.e. reactive oxygen species (ROS)-mediated regulation of immunology and ageing; it brings together the application of small molecule candidate drugs to generate ROS and uses innovative approaches to biomarker identification in models of chronic immune disease. This research has significant potential for application in human health and is of particular relevance to the ageing population. Training, knowledge transfer and skills exchange in this emergent area is important to extend the EU’s reach through cutting edge expertise. Interchange in this way will facilitate and promote early career researcher development into tomorrow’s research leaders. It will encourage new, cross-European collaboration between academia and industry. This tri-partite consortium brings together groups with very complementary expertise for knowledge exchange to benefit early career researchers: ASTON – in the biochemical analyses of ROS; SURREY in thiol oxidation and effects in vitro and ex vivo on and within immune cells relevant for biomarker development in chronic disease; UKER - in animal models of chronic diseases such as systemic lupus erythematosus (SLE) and arthritis; and Redoxis on 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, with a focus on knowledge transfer and drug development. Through future collaborative funding, we anticipate far-reaching applications of redox modulators to manage chronic disease and increase the knowledge of both autoimmunity and ageing of the immune system.