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
Multi-omic analysis of axono-synaptic degeneration in motoneuron disease

Project Coordinator

University Medical Center Göttingen


Magdalena Kuzma-Kozakiewicz Medical University of Warsaw Warsaw, Poland
Jeroen Pasterkamp University Medical Center Utrecht Utrecht, The Netherlands
Valentina Bonetto IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" Milano, Italy
Christine Carapito Institut Pluridisciplinaire Hubert Curien, UMR 7178 - CNRS/Unistra Strasbourg, France
Stefan Bonn University Medical Center Hamburg-Eppendorf Hamburg, Germany
Ralph Schlapbach ETH Zurich Zurich , Switzerland
Reinhold Müller AbbVie GmbH & Co. KG Ludwigshafen, Germany



"Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motoneuron disorder with a poor prognosis and insufficient therapeutic options. Bodyfluid-based biomarkers that could facilitate an earlier diagnosis are not yet available. One of the earliest events in disease development is the degeneration of the synapses and distal axonal segments. A better characterization of this process could lead to development of more efficient therapies.


Here, we first propose to study human tissue and cerebrospinal fluid (CSF) samples and compare these with tissue from transgenic ALS mouse models. Since RNA metabolism plays a crucial role in the pathogenesis of ALS a protein-based approach will not be sufficient to comprehensively characterize disease-relevant pathways. We will thus combine multiple analytic methods from genomics and transcriptomics up to proteomics and metabolomics followed by multivariate semantic data integration to identify new disease-relevant pathways and biomarkers for the disease related to axono-synaptic pathology.


These novel molecular targets will be validated in vitro (e.g. using microfluidic chambers and iPSC cultures), in vivo (e.g. multiple mouse models of ALS) as well as in CSF from ALS patients from a clinical trial cohort. A small molecule library with known and experimental pharmacological compounds from a large pharmaceutical company will be available. Our international consortium of seven established research labs will identify several molecular targets that may open new therapeutic avenues and/or act as biomarkers for earlier diagnosis." 


E-Rare 2012 - Created by Toussaint Biger