Funding for European Spinocerebellar Ataxia Type 3 Disease Initiative (ESMI)

Twenty one research projects have won a total of €35 million (£25.7 million) in a transnational scheme to boost research into neurodegenerative diseases, according to an announcement made by the EU Joint Programme – Neurodegenerative Disease Research (JPND) today. The winning projects will help researchers to better understand, treat and eventually prevent a wide range of debilitating neurodegenerative diseases. Neurodegenerative diseases are one of the toughest medical and economic challenges facing our global community.

The initiative aims to increase coordination of European research efforts in this area and 30 countries currently participate.

European Spinocerebellar Ataxia Type 3 / Machado-Joseph Disease (ESMI)

Coordinator: 

Thomas Klockgether, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE), Bonn, Germany.

Partners:

Paola Giunti, University College London (UCL), United Kingdom
Manuela Lima, University of the Azores Ponta Delgada, Portugal
Luis Pereira de Almeida, University of Coimbra, Portugal
Olaf Rieß, University of Tübingen, Germany
Bart P.C. van de Warrenburg, Radboud University Medical Center Nijmegen, Netherlands

Research proposal 

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is worldwide the most common autosomal dominantly inherited ataxia disorder. 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 approximately 900 subjects. 

The group 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 the initiative will be the development and validation of innovative assessment instruments and disease markers, including a new highly sensitive motor test battery, diffusion-tensor imaging (DTI), automated MRI volumetric evaluation and blood as well as CSF markers based on transcript profiling and disease protein (ataxin-3) measurement. In addition, the impact of lifestyle on disease evolution will be assessed by measuring physical activity with ambulatory sensor-based activity recording and appropriate questionnaires. 

By exploiting the data obtained in this cohort,  a revised model of SCA3 disease evolution will be developed  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. 

The 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 planning and management of this project.