PROSPAX : an integrated multimodal progression chart in spastic ataxias

Joint Transnational Call 2019 (JTC2019)

PROSPAX : an integrated multimodal progression chart in spastic ataxias

Spastic ataxias present an expanding group of >100 rare neurodegenerative diseases with joined damage of cerebellum and corticospinal tract (CST). While rapid genetic stratification facilitates current development of molecular therapies, effective trial-planning for SPAX is hampered by a lack of valid outcome measures and natural history studies. Uniting all major European ataxia and spastic paraplegia networks, and building on our prior networks and pilot data-sets, PROSPAX will establish a paradigmatic IRDiRC-guided integrated trial-ready model of disease progression and mechanistic evolution in SPAX. In a 2-year natural history study we will validate clinician- and patient-reported, digital and molecular outcomes. In addition, PROSPAX will improve existing and develop new outcome parameters that show superior sensitivity to change. These include a novel SPAX composite score, a smartphone mHealth toolbox combining remote assessment of daily living by wearable sensors with app- based patient-entered outcomes, and multimodal MRI radiomics with an innovative machine learning approach for multisite MRI analysis. Longitudinal validation of candidate biomarkers will be complemented by single-cell multi-omic studies in mouse By focusing on the two most prevalent recessive SPAX (SPG7, ARSACS), PROSPAX will create a paradigmatic trial-readiness pathway for charting disease progression and multimodal outcome measures that will be applicable to many of the >100 SPAX diseases alike.

  • Synofzik, Matthis (Coordinator)
    University of Tuebingen [GERMANY]
  • Brais, Bernard
    The Royal Institution for the Advancement of Learning – McGill University [CANADA]

  • van de Warrenburg, Bart
    Radboud University [THE NETHERLANDS]

  • Santorelli, Filippo
    IRCCS Fondazione Stella Maris [ITALY]

  • Elena, Rugarli
    University of Cologne [GERMANY]
  • Nazli, Basak
    Koç University [TURKEY]
  • Tezenaz du Montcel, Sophie
    Sorbonne Université [FRANCE]
  • Horvath, Rita
    University of Cambridge [UNITED KINGDOM]
  • Ataxia Charlevoix-Saguenay Foundation [CANADA]
  • Deutsche Heredo-Ataxie Gesellschaft Bundesverband e.V. (DHAG e.V.) [GERMANY]
  • Euro-HSP [FRANCE]
  • German Research Foundation (DFG), Germany
  • Canadian Institutes of Health Research – Institute of Genetics (CIHR-IG), Canada
  • Fonds de recherche du Québec-Santé (FRQS), Québec (Canada)
  • Netherlands Organization for Health Research and Development (ZonMw), The Netherlands
  • Italian Ministry of Health (MoH-IT), Italy
  • German Research Foundation (DFG), Germany
  • The Scientific and Technological Research Council of Turkey (TUBITAK), Turkey
  • French National Research Agency (ANR), France
  • Own funding
  • INSERM (Linton, Nadke, Gobeil)