Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

The Netherlands
INTEGRative multi-OMICs approaches on iPSC-derived 2D and 3D models to elucidate the role of immune and energy metabolism related genes/pathways in Amyotrophic Lateral Sclerosis

Project Coordinator

IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico


Jeroen Pasterkamp Brain Center Rudolf Magnus Utrecht , The Netherlands
Michela Deleidi DZNE Tübingen, Germany
Philip Van Damme KU Leuven Leuven, Belgium
Stefano Stifani Montreal Neurological Institute Montreal, Canada

Amyotrophic Lateral Sclerosis (ALS) is a rare group of neurological diseases with a tremendous burden on patients and their families, as well as a significant impact on society. ALS is characterized by progressive upper and lower motor neuron (MN) loss due to both cell autonomous and non-autonomous death mechanisms that are largely unknown. Understanding these mechanisms is crucial for developing therapeutics because of the lack of effective treatment for ALS. Based on our previous data showing the role of glial toxicity on MN pathology, we hypothesize that the risk for ALS is associated with alterations in immune and energy metabolism genes/pathways. The main goal of this proposal will be to unravel the role of immune and cell metabolism in ALS pathophysiology by applying integrated multi-omics approaches in relevant ALS models based on induced pluripotent stem cell (iPSC) 2/3D models (mini-brain/spinal cord). To this end, we will: 1) generate and characterize iPSC differentiated cells (MNs and glia) from familial ALS (TDP43/C9) subjects with different clinical phenotypes as well as isogenic (corrected) controls; 2) apply omics approaches (genomic, transcriptomic, proteomic and metabolomic) in ALS-iPSC systems; 3) validate candidate genes/pathways and assess their potential therapeutic role in cell-based platforms. This project involves academic partners with solid expertise in ALS, iPSC technology and omics. This unique combined international effort will allow assessing the role of energy metabolism and immune pathways in ALS pathogenesis and as therapeutic targets.

E-Rare 2012 - Created by Toussaint Biger