Project: PROSPAX: an integrated multimodal progression chart in spastic ataxias
| Acronym | PROSPAX (Reference Number: EJPRD19-193) |
| Project Topic | Spastic ataxias (SPAX) present an expanding group of >100 rare degenerative 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, PROSPAX will establish a paradigmatic IRDiRC-guided integrated trial-ready model of disease progression and mechanistic evolution in SPAX, which will allow to track and understand selective as well as overlapping dysfunction of the cerebellum and CST. In a 2-year transatlantic natural history study we will validate clinician- and patient-reported, digital and molecular outcomes. In addition, PROSPAX will improve on existing and develop new outcome parameters that show superior sensitivity to change. These include a clinical SPAX composite score, a smartphone mHealth toolbox combining wearable sensors with app-based patient-entered outcomes, and multimodal MRI radiomics with an innovative machine learning approach for multisite MRI analysis. Single-cell multi-omic studies in mouse will identify shared pathways and vulnerabilities between cerebellar and corticospinal neurons and will unravel new molecular biomarkers. By example of the two most common 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. |
| Network | EJP RD |
| Call | 1st EJP RD Joint Transnational Call for Rare Diseases Research Project (JTC 2019) |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | University of Tuebingen | Coordinator | Germany |
| 2 | The Royal Institution for the Advancement of Learning – McGill University | Partner | Canada |
| 3 | Radboud University | Partner | Netherlands |
| 4 | IRCCS Fondazione Stella Maris | Partner | Italy |
| 5 | University of Cologne | Partner | Germany |
| 6 | Koç University | Partner | Türkiye |
| 7 | Sorbonne Université | Partner | France |
| 8 | University of Cambridge | Observer | United Kingdom |