TreatHSP

Translational Research in Hereditary Spastic Paraplegias: TreatHSP-net - Teilprojekt 1 (Koordination), Teilprojekt 6

01.05.2019 bis 30.04.2022

Hereditary Spastic Paraplegias (HSP) are clinically and genetically highly heterogeneous neurodegenerative disorders primarily affecting the long axons of the corticospinal tract, leading to progressive lower limb spasticity and weakness. Implementation of causal treatment options is hampered by the genetic and pathophysiological heterogeneity that leads to fragmentation of research efforts. TreatHSP.net will therefore concentrate its translation-oriented research approach on pathophysiological key pathways of HSP (mitochondrial – ER/microtubule-related – endo-lyso-autophagosomal related) that unify multiple and frequent forms of HSP. To make substantial progress towards implementation of novel therapies TreatHSP.net will (i) generate a shared infrastructure that provides federated access to clinical data, biological samples and OMICS data for TreatHSP.net and beyond, (ii) systematically develop and validate outcome parameters for clinical trials including sensor-based, patient- and caregiver-reported as well as molecular outcomes, (iii) use unbiased high-throughput approaches in murine as well as stem cell-derived human models of HSP to identify shared pathways and novel therapeutic targets, and (iv) prioritize drug-repurposing strategies to evaluate novel therapeutic approaches in preclinical trials that promise rapid translatability to human trials.