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Systems Medicine of Mitochondrial Parkinson’s Disease

Objective

The overall objective of this project is to identify novel drug candidates capable of slowing down the progression of neurodegeneration in the subset of Parkinson’s disease (PD) patients with overt mitochondrial dysfunction. Multi-modal phenotypic characterisation of cohorts of monogenic PD patients with overt mitochondrial dysfunction will be used as an anchor for the discovery of two extreme cohorts of idiopathic PD patients: with and without detectable mitochondrial dysfunction. A suite of personalised in vitro, in vivo, and in silico models will be generated using induced pluripotent stem cells (iPSCs) from selected subjects and controls. An industrial quality 3D microfluidic cell culture product, specifically designed for the culture of iPSC-derived dopaminergic neurons, will be developed for use in a morphological and bioanalytical screen for lead compounds reduce mitochondrial dysfunction. By monitoring motor behaviour and in situ striatal neurochemistry at high temporal resolution, the in vivo response to lead compounds will be characterised in humanised mouse models with striatally transplants of iPSC-derived dopaminergic neurons derived from PD patients. Personalised computational models of dopaminergic neuronal metabolism and mitochondrial morphology will be developed. These in silico models will be used to accelerate drug development by prioritising pathways for metabolomic assay optimisation, stratifying idiopathic PD patients by degree of mitochondrial dysfunction, predicting new new targets to reduce mitochondrial dysfunction and mechanistic interpretation in vitro and in vivo experimental results. SysMedPD unites a highly experienced multidisciplinary consortium in an ambitious project to develop and apply a systems biomedicine approach to preclinically identify candidate neuroprotectants, for the estimated 1-2 million people worldwide who suffer from PD with mitochondrial dysfunction.

Call for proposal

H2020-PHC-2014-2015

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Sub call

H2020-PHC-2015-two-stage

Coordinator

UNIVERSITEIT LEIDEN
Net EU contribution
€ 1 201 400,61
Address
Rapenburg 70
2311 EZ Leiden
Netherlands

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Region
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Participants (8)

EURICE EUROPEAN RESEARCH AND PROJECT OFFICE GMBH
Germany
Net EU contribution
€ 386 363,14
Address
Heinrich-hertz-allee 1
66386 St Ingbert

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Saarland Saarland Saarpfalz-Kreis
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
UNIVERSITAET zu LUEBECK
Germany
Net EU contribution
€ 399 262,50
Address
Ratzeburger Allee 160
23562 Lubeck

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Region
Baden-Württemberg Stuttgart Stuttgart, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

UNIVERSITATSKLINIKUM SCHLESWIG-HOLSTEIN
Germany
Net EU contribution
€ 273 250,00
Address
Ratzeburger Allee 160
23562 Lübeck

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Region
Baden-Württemberg Stuttgart Stuttgart, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
UNIVERSITY COLLEGE LONDON
United Kingdom
Net EU contribution
€ 599 978,75
Address
Gower Street
WC1E 6BT London

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
UNIVERSITE DU LUXEMBOURG
Luxembourg
Net EU contribution
€ 1 260 965,00
Address
2 Avenue De L'universite
4365 Esch-sur-alzette

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Region
Luxembourg Luxembourg Luxembourg
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
KHONDRION BV
Netherlands
Net EU contribution
€ 662 500,00
Address
Van Heemstraweg 49 E
6641 AA Beuningen

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Oost-Nederland Gelderland Arnhem/Nijmegen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
MIMETAS BV
Netherlands
Net EU contribution
€ 596 050,00
Address
De Limes 7
2342 DH Oegstgeest

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
NATIONAL UNIVERSITY OF IRELAND MAYNOOTH
Ireland
Net EU contribution
€ 620 220,00
Address
Co Kildare
W23 Maynooth

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Region
Ireland Eastern and Midland Dublin
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00