Joint Transnational Call 2018 (JTC2018)

MAXOMOD

« 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. » 

  • Lingor, Paul (Coordinator)
    University Medical Center Göttingen [GERMANY]
  • Kuzma-Kozakiewicz, Magdalena
    Medical University of Warsaw [POLAND]
  • Pasterkamp, Jeroen
    University Medical Center Utrecht [NETHERLANDS]
  • Bonetto, Valentina
    IRCCS, Istituto di Ricerche Farmacologiche « Mario Negri » [ITALY]
  • Carapito, Christine
    Institut Pluridisciplinaire Hubert Curien UMR –  7178 CNRS/Unistra [FRANCE]
  • Bonn, Stefan
    University Medical Center Hamburg-Eppendorf [GERMANY]
  • Schlapbach, Ralph
    ETH Zurich [GERMANY]
  • Müller, Reinhold
    AbbVie GmbH & Co. KG [GERMANY]