SCA3/MJD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the ATXN3 gene. Even more than 20 years after the identification of the causative gene, neither a causal treatment nor prevention of SCA3/MJD is available. For a successful evaluation of treatment strategy (i.e. to assess the effectiveness of a particular therapy) on the pre-clinical and clinical stage, reliable biomarkers is indispensible especially for slowly progressing neurodegenerative disorders like SCA3/MJD as changes of the biomarker may be much easier (and earlier) measurable (and quantifiable) as e.g. improvement of motor symptoms. It is already known that subjects carrying the SCA3/MJD mutation differ in the onset of symptoms and their clinical subtype. However, less than 50 % of variance in age at onset can be attributed to the length of the repeat expansion. In a Brazilian/German collaborative effort, BIGPRO aims to identify and validate on one hand biomarkers for SCA3/MJD and on the other hand genetic modifiers of the disease. In the prospective study, we will monitor the disease progression in SCA3/MJD patients using clinical scores, videoculography, peripheral proteins and mRNA levels and magnetic resonance imaging of the brain  We then aim to correlate the biochemical, molecular, neurophysiological and neuroimage biomarkers with the clinical scores and will further correlate these findings with identified genetic modifiers. In the cross-sectional study, we will compare our findings between SCA3/MJD patients from different geographical origin / genetic background (Brazil and Germany).

BIGPRO study is being conducted at Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; part of the analyses will be done at University of Tuebingen, Germany. Subjects belonging to the large Rio Grande do Sul SCA3/MJD cohort (Souza et al 2016) were invited to participate. 

Recruitment started in August 2017 and was completed in November 2018. Clinical scales, biological samples, neurophysiological and neuroimaging studies were collected from 90 subjects. The 12 month observations started on August 2018, and the 24 month observations will finish by December 2020.