Final Report Summary - 3DNET (Drug Discovery and Development for Novel Eye Therapeutics) There is an unmet clinical need for more effective treatments to halt or reverse eye diseases that lead to blindness (like age-related macular degeneration, diabetic retinopathy, and corneal inflammation) with increasing prevalence as the EU population ages. Many EU pharmaceutical and biotechnology companies, with established processes for the synthesis and physiochemical characterisation of drugs, have bespoke chemical libraries and lead drugs with potential to treat ocular disease, but lack the expertise and infrastructure to test these drugs in relevant pre-clinical models. In parallel, academic labs with excellent infrastructure to study ocular disease, lack the industry expertise to appropriately develop drugs to enter clinical trials. Thus, clinical development of ocular therapeutics is impeded in the EU due to poor collaboration among academic and industry scientists. 3D-NET (www.ucd.ie/3dnet) established a European network of industry and academic partners, who exchange knowledge, people, and expertise to enhance the discovery and development of drugs that target these ocular pathologies. 3DNET project has been governed by IAPP Marie S. Curie-FP7 Programme, in which the final and overall aim is the international transfer of Knowledge and Technology, achieved through exchange of staff between Industry and Academic sectors. This 4-year project was initiated in September 2013 and finalised in August 2017.In 3DNET, different compounds which might have antiangiogenic (WP1), anti-inflammatory/anti-vascular permeability (WP2) and/or cell-protectant (WP3) activity in the eye, were selected. Resources and expertise of Biologists and Chemists available at each partner have been used synergistically in the consortium to develop novel ocular drugs. Our overall objectives were: 1) Discovery and development of drugs that target ocular pathologies, namely: retinal vascular permeability, unwanted blood vessel growth, inflammation and cell degeneration. Novel ophthalmic drugs will be discovered from unbiased screens of small molecules (random and customised libraries). 2) Avail of 3D-NET consortium capabilities and infrastructure to test these novel drugs in relevant pre-clinical models of ocular disease.In summary, circa 2500 new compounds and analogs have been tested for their efficacy as potential ophthalmic drugs (targeting angiogenesis inflammation, retinal-vascular permeability/RVP and neurodegeneration) on different models (in vivo and in vitro). A number of drug-hits have been further validated (dose dependence, in vitro assays and explants), and 2 novel drug leads are undergoing pre-clinical development. A new RVP-CysLT-induced rodent model has been discovered and validated using gold standard treatments. Additionally, three scientific articles have been published (PMIDs: 25144531, 27086168, 28973338) and there are currently another 4 manuscripts under preparation. Three International Workshops with over 130 attendees have been organised. 1) Coinciding with our first-year general meeting we organized a workshop on “Drug Discovery and Ocular Therapy” (Valladolid, 23/09/2014), at which members of the consortium, external researchers, students and patients got together to learn from each other (www.ucd.ie/3dnet/news/september2014workshop). 2) The "New Frontiers in Ocular Therapeutics" workshop (Dublin 12-13 Oct 2015) brought together clinicians, patients groups, academic scientists (chemists and biologists) and Pharma together to enhance co-operation in this field. Potential new collaborations and joint applications for upcoming H2020 calls were discussed during the meeting (www.ucd.ie/3dnet/news/nfotworkshop). A new successful H2020-RISE application was enabled by NFOT workshop (www.3dneonet.org). 3) A Mini Workshop on “Ophthalmic Drug Innovation, Regulation and Strategies to Reach the Clinical Market”, coincident with 3rd Annual General Meeting (07/September/2016, Nottingham, UK), was hosted by RenaSci.(http://www.ucd.ie/3dnet/outreachactivities/miniworkshopaboutophthalmicdruginnovation2016)The Mid Term Review Meeting of our project was celebrated on Friday 5th of June 2015 in Dublin, hosted by the coordinator Dr Breandan Kennedy in UCD (Conway Institute). The Meeting turned out to be a really enjoyable experience with excellent presentations by fellows and partners, interesting posters and truly constructive discussions. (http://www.ucd.ie/3dnet/news/midtermreviewmeeting).Finally, 3D-NET consortium has taken part in over 20 outreach activities (including ERN-2015) and been featured in at least 18 press releases and Interviews targeting lay audiences (all ages, in Ireland Spain and UK). It has been one of our priorities to convey to the public not only the relevance of scientific research for the progress of the Society and the improvement of living standards, but also the fundamental role of European tax payers to enable projects like 3D-NET.Overall, outputs of 3DNET project (some of them intangible, but proven) have been: a) enhancing intersectoral training, career development and trans-national mobility of EU researchers, b) high impact publications and c) overcoming barriers that impede industry-academia partnership in the EU inhibiting the discovery/development of new-cheaper and more effective drugs for ocular disease. By enhancing the career development of European researchers, creating long-term successful collaboration between industry academia and discovering novel drugs which may improve public health, the 3D-NET consortium has contributed to European excellence and competitiveness.Website: www.ucd.ie/3dnet. Coordinator: Breandan Kennedy (Brendan.kennedy@ucd.ie)
