Project: European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative

Acronym	ESMI (Reference Number: 128)
Duration	01/05/2016 - 30/04/2019
Project Topic	Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is worldwide the most common autosomal dominantly inherited ataxia disorder. It is caused by expansion of polyglutamine encoding CAG repeats in the ATXN3 gene. Currently, there is no treatment for SCA3. However, as there is an advanced understanding of the molecular mechanisms underlying SCA3, new therapeutic approaches are being developed, and the SCA3 field is entering a phase of intense trial activity. To enable interventional trials, availability of large cohorts that consist of preclinical mutation carriers and mildly affected patients is mandatory. For this purpose, the European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative (ESMI) will set up a trial ready cohort by bringing together 7 European cohorts and 1 US cohort, which together comprise more than 800 subjects. We will integrate the existing data in a common database and apply standardized and quality-controlled clinical assessment, MRI and biobanking protocols. A major part of our initiative will be the development and validation of innovative assessment instruments and disease markers, including a new highly sensitive motor test battery, ambulatory sensor-based activity measurement, automated MRI volumetric evaluation, diffusion tensor imaging (DTI), and blood as well as CSF markers based on transcript profiling and disease protein (ataxin-3) measurement. In addition, we will assess the impact of lifestyle on disease evolution by appropriate questionnaires. By exploiting the data obtained in this cohort, we will develop a revised model of SCA3 disease evolution that conceives the preclinical (pre-ataxia) stage and the ataxia stage as the graded manifestation of one disease process, and that will take lifestyle factors into account. Our research directly impacts not only on feasibility and design of interventional trials, but also on routine health care because the new instruments, such as automated activity measurement and MRI analysis, can be used in diagnosis and routine management of ataxia patients. The European and national ataxia patient organizations are directly involved in the planning and management of this project.
Network	JPco-fuND
Call	Neurodegenerative diseases: risk and protective factors, longitudinal cohort approaches and advanced experimental models

Project partner

Number	Name	Role	Country
1	Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)	Coordinator	Germany
2	University College London (UCL)	Partner	United Kingdom
3	University of the Azores	Partner	Portugal
4	University of Coimbra	Partner	Portugal
5	University of Tübingen	Partner	Germany
6	Radboud University Medical Center	Partner	Netherlands