Core groups within PREPARE
Genomics
The genomics core group consists of clinicians and scientists from Tübingen, Paris, Strasbourg, Montreal and Miami. A central part of PREPARE is to screen all genetically still undefined ARCA patients by exome sequencing, thus maximizing the number of patients eligible for treatment trials and elucidating novel ARCA syndromes. Moreover, PREPARE has launched the Ataxia NGS consortium, which is the world’s largest repository of next-generation sequencing datasets (large NGS panels, whole exome, whole genome) of ataxia patients, already aggregating NGS datasets from >600 ataxia patients. The Ataxia NGS consortium exploits the multicenter web-based automated high-throughput analysis pipeline GENESIS which allows for joint NGS data aggregation and data analysis by all partners of the PREPARE consortium.
Animal Models
The core for animal models is formed by Nijmege, Illkirch and Montreal.
Drosophila models of ARCAs
Another rapid and powerful, yet already more complex model system are Zebrafish models. First Zebrafish models of ARCAs have been generated by the Illkirch partner.
Zebrafish models of ARCAs
Another rapid and powerful, yet already more complex model system are Zebrafish models. First Zebrafish models of ARCAs have been generated by the Illkirch partner.
Mouse models of ARCAs
PREPARE exploits knockout mouse models for the prototypical ARCAs that have been selected as the first paradigmatic ataxias that will be made trial-ready: Autosomal-Recessive Spastic Ataxia of Charlevoix Saguenay (Montreal, Canada) and ADCK3/COQ8A- ataxia (Illkirch, France).
These models complement and inform the clinical and biomarker profiling on human ARSACS and ADCK3/COQ8A-ataxia. Furthermore, we embark on pre-clinical trials with candidate compounds using these two animal models, while also drafting guidelines for future trials for other ARCA mice models.
Biomarker
The Biomarker core consists of clinicians and researchers from Tübingen, Pisa and Illkirch. We follow a genuine trans-species approach by investigating biomarkers in parallel in both animal models as well as human biomaterials. Blood (plasma, serum, DNA, RNA, Dried Blood Spots), urine and CSF samples are collected across the whole consortium and by associated partners using standardized protocols, thus yielding the largest ARCA biobank repository worldwide.
Clinical - Outcome Measure
The clinical core group aims to establish reliable and valid outcome measures for future ARCA treatment trials, already implementing and testing them in a multi-center fashion in the major ARCA centers worldwide. The clinical core group consists of clinicians and physiotherapists with clinical and trial expertise in genetic ARCAs. Clinical outcome measures are established by an international collaborative process, capturing complex ARCA phenotypes. As a paradigmatic model, we will first focus on ARSACS, with other recessive ataxias to follow (ADCK3/COQ8A, SPG7, etc).