Objectives

Our overall objective is to further explore and identify novel drug candidates capable of slowing down the progression of neurodegeneration in the subset of PD patients with overt mitochondrial dysfunction.

Equipped with a budget of €5.9 million, we will improve means for PD detection and therapy development, will commercialise the project results so the society as a whole can benefit from the results and will leverage national and European investments in the systems biomedicine sector to build up a strong European systems medicine community.

Approach

The SysMedPD consortium pursues an interdisciplinary research approach bringing together clinical research, engineering and computational biology. The project consists of five scientific work packages:

WP 1 – Clinical
Establishment of a monogenic PD cohort and generation of a Mito-IPD cohort, each sharing the mitochondrial PD signature. This will help to focus on subsequent preclinical model development and the application of these models to develop new therapeutic candidates on mitochondrial dysfunction in PD.
Work package leader: University of Luebeck, Germany
WP 2 – In vitro
In vitro testing of repurposed mitochondrial compounds that rescue mitochondrial dysfunction in phenotypically verified microfluidic cell cultures of iPSC-derived dopaminergic neurons
Work package leader: Mimetas BV, The Netherlands
WP 3 – In vivo
Behavioral and neurochemical evaluation of the most promising compounds (identified from in vitro testing) in humanised mice
Work package leader: Maynooth University, Ireland
WP 4 – Assay
Development and validation of a target engagement biomarker for PD with mitochondrial dysfunction to improve the design of future clinical trials for Mito-PD
Work package leader: Leiden University, The Netherlands
WP 5 – In silico
Conversion of the metabolic-mitochondrial reconstruction into a constraint-based computational model that can be used to predict biochemical reaction rates
Work package leader: University of Luxembourg, Luxembourg

Two additional work packages act to support these scientific objectives:

WP 6 – Management and Coordination
Maximized effectiveness of project activities: ensuring the timely and qualitative achievement of project results through scientific and administrative coordination.
Work package leader: University of Luxembourg, Luxembourg
WP 7 – Dissemination and Exploitation
Creation of visibility and encouraging the project outreach, strengthening of innovation and exploitation of results.
Work package leader: European Research and Project Office GmbH, Germany