The Project


The PREPARE project is divided into 5 work packages (WP).

  • Our shared prospective web-based longitudinal registry allows to aggregate ARCA trial-ready cohorts of sufficient size and establish serial natural history data needed to launch treatment trials (WP1). It will present the world’s largest clinical ARCA patient registry.
  • Genetically still undefined ARCA patients will be screened by exome sequencing, thus maximizing the number of patients eligible for treatment trials and including definition of novel ARCA genes (WP2). All exomes will become part of the Ataxia NGS consortium, which will be the world’s largest aggregation of NGS datasets from ataxia patients.
  • To support causality of the novel genes and to identify pathway nodes susceptible to drug compounds, genetic fly models will be created (WP3).
  • Trial outcome measures will be established by a stringent, FDA-conform international collaborative process, capturing the multisystemic complexity ARCA phenotypes and including extensive „3-omics“ biomarker screening (WP4). It will hereby draw on the ARCA biobank repository, which aggregates biomaterials from ARCA patients across the world.
  • First preclinical trial protocols applicable to many ARCA types will be implemented in transgenic ARCA mice, including testing of drug compounds (WP5).

This translational pipeline will first be tested in two paradigmatic autosomal-recessive ataxias, namely Autosomal-Recessive Spastic Ataxia of Charlevoix Saguenay (ARSACS) and ADCK3/COQ8A- ataxia. If successful, other autosomal-recessive ataxias, like e.g. SPG7-ataxia, will follow.