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EVOluTION Report Summary

Project ID: 675111
Funded under: H2020-EU.1.3.1.

Periodic Reporting for period 1 - EVOluTION (European Vascular Interventions and Therapeutic Innovation Network)

Reporting period: 2016-04-01 to 2018-03-31

Summary of the context and overall objectives of the project

EVOluTION (European Vascular Interventions and Therapeutic Innovation Network) is a pioneering innovative training network (ITN) designed to provide multidisciplinary training for 11 Early Stage Researchers (ESRs) on the biology of endogenous mechanisms that protect our vasculature. This network has been established to create innovative therapeutic strategies for the chronic diseases that affect the ageing population of Western societies. There is an acute need for new medicines to treat chronic widespread high penetrance diseases of the Western world. Despite large investments in drug development (€ 1.2 billion is the current estimate for completing the bench to bed path), the majority of compounds fail to make it to the clinic. This occurs against a background where current therapies are burdened, especially on chronic administration, by substantial side effects that limit their use and efficacy. To fill this gap, EVOluTION has created a doctorate programme to deliver innovative training on preclinical and clinical science, commercial and business aspects, intellectual properties and more, covering the multiple aspects of the drug discovery and development process. The scientific response to the unmet need is a focus on endogenous tissue protective mediators and pathways as a new way to therapeutic innovation: therapeutic strategies developed on the processes operative in our body to heal and repair will be innovative in their mode of action. EVOluTION provides a conducive structure formed by 5 leading academic institutions and a number of pharma and biotech companies. The scientific and educational expertise of the beneficiaries and partners, leaders in areas like computational chemistry, nutraceuticals, resolution pharmacology and vascular protection has enabled an innovative and transformational programme.This ITN aims to deliver high-level scientific and complementary training, forging career pathways to increase inter-sectorial and trans-national employability of young entrepreneurially-minded scientists in the academic and non-academic public and private sectors. This will create a future cadre of European leaders in scientific and aligned disciplines, for the benefit of society at large.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The research developed in this programme is based on the concept that endogenous processes and mediators are processes operative to protect our body, with a focus on the vasculature as a shared conduit, central to multiple chronic diseases. The 11 Early Stage Researchers are focused on projects that span 4 key areas (work packages; WP) of endogenous tissue protection:WP1- Mechanisms by which dietary approaches boost protection, WP2- Endogenous tissue protective mediators, WP3- Pro-resolving receptors, WP4- Proof of concept approaches for innovative therapeutics. In WP1, ESRs are providing proof of concept experimentation on how dietary intervention can boost endogenous tissue protection, focusing on vascular pathways. Promising results are emerging on the role of nitrate on longevity, hypertension and metabolic function. Compounds that inhibit a key enzyme involved in nitrate catabolism have been identified and will be characterised to determine their effect in vivo. Studies on the effect of dietary interventions on platelet reactivity indicate the importance of fatty acids in platelet aggregation. In the area of endogenous tissue protective mediators (WP2), the first research milestone has been reached with identification of the complete molecular signature of macrophages in atherosclerosis. These novel targets will be used to develop strategies for the re-programming of the atherosclerotic plaque. Such an aspiration underlies research in vascular calcification, the major reason for death in kidney disease, with an innovative focus on mechanisms that control the release of extracellular vesicles. In the final project linked to this research objective the molecular determinants regulating leukocyte-endothelium interactions in blood vessels of the inflamed brain after stroke and the effect of inhaled nitric oxide are being investigated. Data produced to date reveal that inhaled nitric oxide inhibits the neuro-inflammatory response after ischaemic stroke. The objective of WP3 is more pharmacological in its nature, focusing on i) the expression of specific pro-resolving receptors following selected dietary intakes and ii) their activation through synthetic therapeutics. Pro-resolving receptors involved in diabetic nephropathy are being targeted and a number of synthetic mimetic compounds have been identified and are currently being tested for their efficacy to modulate inflammation in vivo. Pro-resolving receptors associated with atherosclerosis are being targeted as an approach to develop novel therapeutic strategies to treat this disease. In the final key research area (WP4), novel approaches will be applied to target the vasculature and ameliorate disease. One of the projects aims to characterise natural vesicles as a tracer for inflammatory events in the vasculature, possibly also to be developed into a therapeutic tool. As such, a number of candidate markers have been identified in microparticles derived from monocytes to reflect the incidence of monocyte/platelet aggregation. In a second project, the bio-actions of vitamin K and vitamin K antagonists on vascular smooth muscle cell oxidative stress, senescence, and apoptosis are currently being investigated. The most active vitamin K derivatives will be selected as a suitable therapeutic tool to regulate vascular smooth muscle cell homeostasis and calcification.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

EVOluTION will generate skilled and dedicated researchers that will become future entrepreneurially-minded scientific leaders equipped with complementary skills and a deep understanding on how disease prevention and health promotion can be maximally exploited in patients. The scientific results produced from the programme will form an important base to identify novel therapeutic tools and strategies that could be utilised in treating various chronic diseases, including diabetic nephropathies and cardiovascular disease.
The four main impacts of this Action are to: 1) Realise the potential of individual researchers and enable new career perspectives by providing research and innovation related human resources, skills and training in world class working environments. 2) Develop sustainable partnerships between academia and industry, facilitating the translational research process from bench to clinic.3) Effectively communicate and disseminate the results to other researchers and the wider public. 4) Exploit the results and intellectual property. These impacts will encompass and benefit the wider socioeconomic field by potentially providing new therapeutic strategies for the treatment of chronic diseases, and by educating both researchers and the wider public that we can harness the body’s endogenous mechanisms to prevent and treat many different diseases that are affecting the western world today. Moreover, on top of scientific training and knowhow, EVOluTION will equip the ESRs enrolled in the programme with business and entrepreneurial skills to push forward their results and translate them into beneficial approaches, if not treatments, to alleviate the debilitating consequences of chronic disease.

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