Euro-SCAR

The present project will focus on the non-Friedreich’s ataxias, by designing an efficient screening methodology for degenerative recessive ataxias (DRA) using high-throughput sequencing of 30 DRA genes. Due to this broad approach, we will be able to gain knowledge about the frequency of all DRAs in different European populations as well as the phenotypic variability of single entities. To this end, patients will participate in neuroimaging studies using structural, functional and diffusion tensor imaging. Furthermore, this genetically well-defined cohort will provide an ideal basis in search for new autosomal recessive ataxia genes. Large families with ataxia corresponding to none of the known forms will be used to identify the corresponding molecular defects. Patients with novel recessive ataxia will participate in neuroimaging studies using structural, functional and diffusion tensor imaging. Once a new gene is identified, if it is evolutionarily conserved, validation of mutations will be carried out in yeast, Caenorhabditis elegans and/or zebrafish models. Induced pluripotent stem cells will be generated for these new forms of ataxia in order to test the molecular pathways involved in these diseases (oxidative stress, genotoxic stress, metabolic stress…). Additionally, this approach will promote interventional trials in ataxia subtypes where therapeutical strategies are already available by identifying respective families and gathering representative cohorts of these rare diseases.