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Initial Training Network on therapeutic approaches and predictive models for neurodegenerative diseases

Final Report Summary - NEUROMODEL (Initial Training Network on therapeutic approaches and predictive models for neurodegenerative diseases)

Initial Training Network (ITN) on therapeutic approaches and predictive models for neurodegenerative diseases (NEUROMODEL)

Project objectives

The aim of the NEUROMODEL network is to address the three most important bottlenecks for finding more effective medicine in brain disorders, mainly Parkinson's disease and Huntington's disease:

(1) identification and validation of pre-symptomatic and surrogate markers for disease progression;
(2) development of model systems that translate to human pathology and are predictive of clinical efficacy; and
(3) better understanding of disease mechanisms leading to better target selection.
Therefore, we have assembled a unique consortium of five industrial and five academic partners to achieve both organisation of an excellent training program and performance of excellent research projects with a pronounced focus on intersectional transfer of knowledge.

Building on the expertise gathered in the NEUROMODEL network, it is also the objective of the network to train young researchers to be fully prepared to meet the increasing demands for multiple skills of the European (scientific) labour market. NEUROMODEL has implemented a comprehensive training programme that is composed of four levels:

(1) academic and industrial training;
(2) training in scientific and complementary skills;
(3) local and network wide European training; and
(4) scientific in-depth training focused on a specific topic of a PhD thesis and broad spectrum training covering the various sub-disciplines of translational research.

Work performed since the beginning of the project

All partners recruited fellows who enthusiastically worked on their projects and revealed promising results. Two PhDs were already awarded. Scientific needs of the project made it a must to engage in (inter-sectoral) collaborations, e.g. by providing animals or lab space and assistance for biochemical analyses. Beside their individual projects, all fellows engaged in network-wide training events covering both scientific topics and complementary skill training. A mutual recognition of the training performed was acquired wherever possible.

The NEUROMODEL website (see http// online) was established to raise the public awareness of the NEUROMODEL project. This web site also contains internal pages that are used as a teaching and reference tool for the fellows, contain material from the training weeks, annual presentations etc.

All partners of the consortium met regularly for presentation of results and fruitful discussions.

Main results achieved

The NEUROMODEL consortium contributed to find more effective medicine in brain disorders, namely Parkinson (PD) and Huntington disease (HD) on several levels:

First of all, animal models with high predictive value are a prerequisite for translational research. Regarding PD, the consortium developed and validated a new viral-vector based mouse model and optimise d a lesion mouse model for PD, and managed to validate a recently developed bacterial artificial chromosome (BAC) rat model for HD. Beside the overt symptoms, the consortium was able to reveal several pre-manifest behavioural alterations, like schizophrenia-like traits.

Secondly, the consortium aimed to refine animal testing, both in the light of standardisation, translation to the human diseases and animal welfare. Existing tests were optimise d, and potential influencing factors like housing conditions were validated. Innovative testing of rat and mouse models in automated cages, including improved data processing and analysis, was improved and revealed early symptoms in animal models. Techniques established can easily be transferred to other diseases.

Finally, new targets for therapeutic approaches should be revealed. For PD, NEUROMODEL confirmed that protein degradation is involved in PD development and identified novel targets for the symptomatic and neuroprotective treatment of PD. Furthermore, a new advanced technology was developed to study physiology and morphology in small, spinal striatal neurons. For HD, several novel targets with therapeutic relevance were detected, while others have to be refused. An innovative duplex assay to measure simultaneously soluble and aggregated Huntingtin protein (mHtt) was developed that enables monitoring of treatment efficacy in drug development. The aforementioned findings resulted in 13 peer-reviewed publications so far; several others are in preparation or submitted. Results were presented at several international conferences. Fellows also presented their work to the general public (outreach activity).

Beside the scientific objectives, the NEUROMODEL consortium achieved its aim to train young researchers to be fully prepared to meet the increasing demands for multiple skills of the European (scientific) labour market. Local scientific in-depth training was complemented by a broad network-wide training with a strong focus on academic-industrial collaboration and complementary skills.

Potential impact and use

The NEUROMODEL project educated well-trained young scientists. This does not only apply to the high-ranking PhD theses due to excellent research projects. Together with the inter-sectoral working experience in both academic and industrial partners, a broad-ranging scientific training enabling a 'look over the rim of the plate', and the complementary skill training, the fellows are perfectly prepared to meet the demands of the European job market.

Given the devastating nature of PD and HD and lack of disease modifying treatments, there is great need for finding effective treatment. NEUROMODEL contributed to this objective with considerable success by deciphering pathological pathways of the diseases, using newly-developed innovative animal and cellular models and sophisticated tools for analysis. Possible therapeutic targets for both diseases were revealed and investigated. The NEUROMODEL network significantly increased the collaborations between the partners with a focus on academic-industrial networking.

Socio-economic impact and the wider societal implications of the project

Neurodegenerative brain diseases constitute a major health problem in Europe, and their impact on public health and society is increasing with the aging of the population. The NEUROMODEL consortium successfully contributed to the challenge to develop new therapeutic approaches by developing valid disease models and sophisticated tools for their analysis. The latter will not only reduce time but also costs for drug development, and will help to improve animal welfare. Furthermore, a number of promising therapeutic approaches for both PD and HD were revealed. Findings are not only relevant for academic groups working on neurodegeneration, but also for companies engaged in central nervous system drug discovery. The work provided within NEUROMODEL will impact patients, care takers and patients' families significantly, however, would certainly need another ten years or so to reach the patients.

Apart from the scientific results that were presented both to the scientific community and - via the outreach activity - to a wider public, NEUROMODEL succeeded to train 12 promising scientists to meet the challenging demands of the European job market.