Introduction

European integrated project on spinocerebellar ataxias (EUROSCA):
Pathogenesis, genetics, animal models and therapy

Twenty two European groups from 9 countries with an excellent reputation of clinical, clinical-genetic and basic research on spinocerebellar ataxias (SCA) jointly form an “Integrated project” to develop a treatment for patients suffering from this rare, late manifesting, and autosomal dominant inherited group of neurodegenerative diseases. To reach this goal, an international standard on the clinical evaluation in form of a “Core Assessment Program for Interventional Therapies of SCA (CAPIT-SCA) will be developed based on clinical rating scales, structural imaging, and electrophysiology. The generation of the world largest collection of information on SCA, the European SCA Registry (EUROSCA-R), will ensure standardized data acquisition. This powerful tool will facilitate continuous recruitment of SCA patients throughout Europe for linkage analysis, identification of novel ataxia genes and natural history studies. The potential to include all larger European SCA families into linkage analysis will lead to the identification of new SCA loci and to the cloning of novel ataxia genes such as for SCA4, SCA11, SCA13, SCA14, and SCA21, respectively. Genotype-phenotype correlations will follow. Subsequently, for the first time such a combined effort will offer a systematic large scale search for genetic modifier factors in SCA allowing a better comprehension of factors accounting for wide clinical variability with application for prognosis and to identify new potential targets (modifier genes) for delaying the age at onset or disease progression. EUROSCA will also implement strong research projects to generate and characterize cellular and transgenic models, which will allow a more defined study of the pathogenesis and will serve as a tool for first therapeutic studies. Nine European research groups are supported by five core facilities such as transgenic Drosophila work, Expression-Chip-Technology, Proteomics, yeast two hybrid technology, and monoclonal antibody production to increase competition to groups in the US and Japan. Training programs will complement research efforts and clinical work. An elected board of experts guaranties efficient management with clear responsibilities.