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European Vascular Interventions and Therapeutic Innovation Network

Periodic Reporting for period 2 - EVOluTION (European Vascular Interventions and Therapeutic Innovation Network)

Reporting period: 2018-04-01 to 2020-03-31

EVOluTION, the European Vascular Intervention and Therapeutic Innovation Network, has trained 11 ESRs in endogenous mechanisms of tissue protection, harnessing the vasculature as the common conduit with an impact on a variety of diseases, from hypertension to vascular calcification, from atherosclerosis to myocardial infarction and kidney disease. What does it mean? We have trained on and studied mechanisms that are important for our physiological well-being with the aim of exploiting them for innovative therapeutic approaches to treat several chronic pathologies that affect our society. Thus, the underpinning objective of this ITN is to harness what we can learn from physiology (health), and what we can exploit from this knowledge (innovation) to develop new therapies for pathology (disease).

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 needs identified by EVOluTION consortium is a focus on endogenous tissue protective mediators and pathways as a way that could guide the development of innovate therapeutic approaches: therapeutic strategies based on the processes operative in our body to heal and repair will be innovative in their mode of action. With EVOluTION a conducive structure formed by 5 leading academic institutions and a number of pharma and biotech companies was formed. 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 has delivered 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. The long-term objective was to train high-calibre early stage researchers and create a future cadre of European leaders in scientific and aligned disciplines, for the benefit of society at large. The knowledge that scientific training and know-how can benefit society not exclusively when applied in a laboratory, academic or industrial, but also in several other career paths has been a major drive for this ITN.
EVOluTION (European Vascular Interventions and Therapeutic Innovation Network) has been 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. The projects of the Early Stage Researchers span 4 key areas (work packages; WP) to study and exploit endogenous tissue protection:

WP1- use of dietary approaches to boost protective mediators and pathways
WP2- Study these endogenous tissue protective mediators
WP3- Utilise the targets for these protective mediators to device new therapies
WP4- Proof of concept approaches for innovative therapeutics

In WP1, ESRs have provided proof of concept experimentation on how dietary intervention helps our body to deal with diseases, including nitrate and fatty acids. The focus has been on ageing and hypertension, as well as vascular thrombosis and we demonstrated that this fatty acid reduced platelet activation and unveiled the specific mechanisms by which this occurred, opening therapeutic opportunities against thrombosis. WP2 is strongly associated with WP1, and in fact we have used nitric oxide itself as a therapy to study its effect on cellular events in our blood vessels and how this is beneficial against stroke. Using modelling and computer plus mathematical approaches we have studied interventions that could limit vascular calcification, discovering a set of new structures of pharmacological interest. Finally, we studied what can be applied to control, block and possibly revert atherosclerosis to help future drug discovery programmes. The objective of WP3 has been more pharmacological in its nature. Here we have tested novel molecules modelled on pro-resolving mediators to define their fundamental pharmacology in the context of diabetes-induced kidney disease, sepsis and myocardial infarct. In WP4, novel approaches were applied to target the vasculature and ameliorate disease. Here the efforts of the consortium were directed at providing proof-of-concept for novel therapies, making this WP a true complement to WP3. Natural nanomedicines have been identified, characterised for their ingredients and tested on atherosclerotic plaque. The results obtained explain the protection afforded by vitamin K analogues against vascular calcification, the ‘lethal event’ typical of chronic kidney disease and other pathologies typical of our society. Novel small molecules were also drawn, synthesised and tested in WP1 and WP3.

In summary, albeit by and large at the preclinical level but when possible corroborated with human tissues and human analyses, EVOluTION has taken directly on the challenge to be innovative on how we can impact on ageing, hypertension and thrombosis (WP1: using nutrition programmes), vascular pathologies like stroke, vascular calcification and atherosclerosis (WP2 and WP4), diabetes and infarct (WP3).

We have been highly active in disseminating the results produced with the ITN producing at the end of the financial period 35 conference presentations, 7 travel awards won, 10 prizes awarded for poster and/or oral presentations, and finally 13 publications. These bring the total dissemination KPIs at project end to 66 conference presentations and 16 publications, between the 11 EVOluTION ESRs. In addition, three ESRs have now defended their post-doctoral theses with success.

Close attention has been paid to the exploitation pathway, and this included training of the early stage researchers on intellectual property creation and protection, commercialization and licencing strategies, together with the practical application of this knowledge to specific projects. It is predicted that exploitation will continue to be attained, and monitored, well beyond the end of the Action.
EVOluTION has generated 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 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.
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