Project: Identification of molecules to treat Parkinson’s disease (PD) using a novel zebrafish model

The PARK project is set at the discovery stage of the biopharmaceutical drug development chain and aims at identifying chemical compounds that have the ability to protect/reverse Parkinson’s -like phenotypes in an in vivo vertebrate background that will also be developed in the context of the project. These compounds will enter the market of therapeutics for Parkinson’s disease (PD), upon preclinical and clinical studies. _x000D__x000D_The project consortium is composed of one SME and three academic institutions. It gathers the best of the industry-academic Pships in order to research and develop the most innovative and technologically advanced products in the biomedical field of PD. _x000D_TechnoPhage, the SME, is a biopharmaceutical company engaged in the research and development of therapeutics and diagnostics with programmes in areas such as oncology, inflammation, bacterial infection and bone disorders. Erasmus MC is a University-Hospital focused on research, education and healthcare in biomedicine. The Associação para a Investigação e Desenvolvimento da Fac. de Medicina (AIDFM) is the Association that manages R&D projects from researchers of the Faculty of Medicine of the University of Lisbon. The Fac. de Engenharia da Univ. do Porto (FEUP) is a research and education Institution devoted to Engineering. _x000D_The Consortium will generate both a biological tool (transgenic zebrafish models of PD) and a biosensor to assess fish behaviour in order to produce a set up to screen for compounds that will hopefully be used in PD therapeutics. ErasmusMC and the AIDFM will generate the transgenic animal models of Parkinson Disease and validate their bona fide reproducibility of Parkinson-like characteristics both at cellular and molecular levels. The AIDFM and FEUP will develop a biosensor to assess behaviours of whole vertebrate organisms in vivo. The SME will take the compounds identified in this project into preclinical studies and subsequent clinical trials in the two years after the end of the consortium. These compounds are aimed at the PD market of therapeutics. The zebrafish and the biosensor will be commercially exploited by the academic institutions. _x000D__x000D_Technical applications:_x000D_This project will identify molecules that are able to act on the molecular mechanisms that lead to PD. The path to the discovery of such compounds will lead also to the generation of novel PD animal models that both increase our understanding of the disease at cellular and molecular levels and also enable an innovative tool that will be crucial in drug discovery with significant impact in the future of therapeutics of PD patients. In addition, the project will generate an electrical biosensor that will provide a technically advanced and innovative manner to assess behaviour and potential toxicity of agents on vertebrate organisms in vivo. _x000D_Market applications:_x000D_Given the focus of the project on PD, all products have a potential application on the PD-related industries. _x000D_PD (PD) is the second most common neurological disorder, affecting approximately 4.1m people worldwide. As the prevalence rate of PD is set to rise significantly in the coming years, clinical interventions will play a major role in combating the wide spectrum of unmet needs associated with the disease. _x000D_In 2006, the global sales of PD therapeutics were $3.1bn up by 11% from $2.5bn in 2005. Revenues of the only approved PD drugs across the major markets (US, Japan, France, Germany, Italy, Spain and the UK) totalled over $2.2bn in 2006, with revenues expected to exceed $4.6bn by 2012. With key PD drugs expected to lose patent in the near-term, new products will be strongly sought by this market._x000D_The project will generate three products with a potential market application and target. All of them have a clear focus on PD-related industries. _x000D_First, a transgenic vertebrate animal zebrafish model for PD will be generated. In fact, this model corresponds to two independent products because the transgenics will involve two different genes. Because there is no such model on the market, both the biomedical research industry and the pharmaceutical industry will seek the use of such animal model. The value associated with this model may therefore be very high. _x000D_Second, the consortium will generate a biosensor to assess zebrafish behaviour and locomotor activity. In addition, this biosensor provides physiologically relevant information such as cardiac beating and ventilation frequency that is used to assess toxicity, a major constraint in successful drug development. Thus, this product has a definite potential high value in the drug discovery industry, from biotech to pharmaceutical industry. _x000D_Third, agents that may treat PD will also be generated by this Consortium. These compounds will be taken into preclinical studies after the end of the consortium and subsequent clinical trials. These products target therefore the pharmaceutical industry in the therapeutics for Parkinson’s disease. _x000D__x000D__x000D_

Acronym PARK (Reference Number: 5553)
Duration 01/10/2010 - 30/06/2014
Project Topic This project will deliver candidate-molecules for PD. We will develop both a novel zebrafish model of PD, and a novel system to assess behaviour. We will reduce costs and increase efficiency in drug development by using these tools to screen a chemical library in search for new therapeutics for PD.
Project Results
(after finalisation)
WP1 lead to the successful generation of a transgenic line overexpression human alfa- synuclein gene with a confirmed cellular and behavioral phenotype, which is expected to mimic PD phenotype. The consortium consider that the line nestin:EGFP-2A-SNCAwt-cmcl2:mCherry is the most promising line to mimic PD and is preparing a manuscript with all the data. In the future this line can be used to screen new candidate molecules for PD treatment, as well as, be used to study disease mechanisms related with synuclein overexpression/aggregation. This WP was performed by IMM, EC and TechnoPhage.
Network Eurostars
Call Eurostars Cut-Off 4

Project partner

Number Name Role Country
5 TechnoPhage, S.A., Investigação e Desenvolvimento em Biotecnologia Coordinator Portugal
5 EDIGMA COM, Gestao de Projectos Digitais, SA Partner Portugal
5 Instituto de Medicina Molecular Partner Portugal
5 Fundação da Universidade do Porto - Faculdade de Engenharia Partner Portugal
5 Erasmus University Medical Center Rotterdam Partner Netherlands