European Spinocerebellar Ataxia Type 3/Machado*Joseph Disease Initiative

SCA3 is the most common dominant form of cerebellar ataxia. 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.

To set up a trial*ready cohort by bringing together 7 European cohorts and 1 US
cohort
and include new subjects, which together comprise more than 800 subjects with
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.

Study design: An observational cohort study

Patients will visit the local partner once a year for three consecutive years.
These visits includes clinical assessment which includes validated ataxia*
scales and tests to assess cognitive function, mood, activities of daily living
and quality of life. Blood samples will be acquired at each visit in a
subset of patients. This results in a total of 3 blood samples for 15 patients
during the study. In a subgroup of 60 SCA3 mutation carriers, and a subset
thereof (estimated 15*20 subjects) in the Netherlands, detailed quantitative
motor assessment will be performed. At about half of these visits
new MRI scan will be acquired according to that needs about 35 minutes to be
completed. Controls will only receive clinical assessment and blood sampling.
Optionally, patients will be asked to undergo a lumbar puncture.