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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.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/basic medicine/neurology/parkinson

Call for proposal

H2020-PHC-2015-two-stage
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

UNIVERSITEIT LEIDEN
Address
Rapenburg 70
2311 EZ Leiden
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 201 400,61

Participants (7)

EURICE EUROPEAN RESEARCH AND PROJECT OFFICE GMBH
Germany
EU contribution
€ 386 363,14
Address
Heinrich-hertz-allee 1
66386 St Ingbert
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
UNIVERSITAET zu LUEBECK
Germany
EU contribution
€ 672 512,50
Address
Ratzeburger Allee 160
23562 Lubeck
Activity type
Higher or Secondary Education Establishments
UNIVERSITY COLLEGE LONDON
United Kingdom
EU contribution
€ 599 978,75
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
UNIVERSITE DU LUXEMBOURG
Luxembourg
EU contribution
€ 1 260 965
Address
2 Avenue De L'universite
4365 Esch-sur-alzette
Activity type
Higher or Secondary Education Establishments
KHONDRION BV
Netherlands
EU contribution
€ 662 500
Address
Van Heemstraweg 49 E
6641 AA Beuningen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
MIMETAS BV
Netherlands
EU contribution
€ 596 050
Address
Jh Oortweg 19
2333CH Leiden
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
NATIONAL UNIVERSITY OF IRELAND MAYNOOTH
Ireland
EU contribution
€ 620 220
Address
Co Kildare
W23 Maynooth
Activity type
Higher or Secondary Education Establishments