Natural history and biomarker identification in Spinocerebellar Ataxia type 7

SCA7 is a rare, genetic, currently untreatable neurological disorder that leads
to immobility and blindness. The chance the gene is passed on to children is
50%. The brain abnormality in SCA7 is mostly found in the cerebellum, but other
areas are also affected, as is the eye. The cause of these abnormalities is an
error in the ataxin-7 protein.

Currently patients are treated symptomatically, which often is ineffective
against progressive loss of mobility and independence, eventually leading to an
early death. There are high expectations for the development of a genetic
therapy that could halt the disease progression. The low number of SCA7
patients makes it essential to have sensitive surrogate markers for disease
progression. Validated clinical parameters are present for ataxia, but their
interaction and sensitivity in SCA7 are unknown. There is a lack of biomarkers
for SCA7, but the availability of these is essential for trials in rare
diseases. This study will therfore develop and validate biomarkers for SCA7 as
well as map the disease progression of this disorder.

Primary objective:
- To identify (a combined set of) clinical and non-clinical markers most
sensitive to disease progression in Dtuch SCA7 mutation carriers.

Secondary objectives:
- To quantify the annual change in disease-relevant clinical scales and
patient-reported outcome measures in SCA7 patients.
- To establish the utility of ophthalmologic assessment analysis as a surrogate
biomarker in SCA7.
- To establish the utility of MR measures as surrogate disease progression
markers in SCA7.
- To develop and establish the utility of biochemical disease and progression
markers.
- To establish the utility of automated gait analysis as surrogate biomarker in
SCA7.
- To generate a natural history data set of clinical parameters, MRI,
ophthalmologic, and biochemical biomarker measurements in SCA7 that can be
exploited for further collaborative research in SCA7.


To reach trial-readiness

A prospective cohort study will capture the natural history of Dutch SCA7
patients over the course of one year. We will include 20 SCA7 patients and 20
matched controls. All study participants will undergo detailed annual
assessments at baseline and 1 year after baseline.

The age matched controls will be recruited from an already existing cohort of
controls for SCA1, they will be asked formal consent for the use of their data
for the SCA7 study. If needed the existing cohort will be enriched with new
controls recruited for the SCA7 study.

Deelnemers bezoeken het studiecentrul eenmaal per jaar, gedurende 1 jaar (2
bezoeken in totaal). Deze bezoeken omvatten voor alle deelnemers een klinisch
onderzoek, MRI scan (45 minuten), looptesten, oogheelkundig onderzoek,
bloedmonsters, en vragenlijsten. Patiënten kunnen tevens kiezen om mee te doen
aan het optionele onderdeel om tweemaal een lumbaalpunctie te ondergaan.

Participants will visit the study centre once a year for one year. These two
visits include a clinical assessment battery, including validated ataxia-scales
and tests to assess cognitive function, mood, activities of daily living.
Ophthalmologic assessment, MRI-scans (45 minutes) and blood samples will be
acquired at each visit. Patients will be asked to optionally undergo a lumbar
puncture twice (baseline and after 1 year), to obtain a cerebrospinal fluid
sample. Controls will receive a similar assessment protocol, without the lumbar
puncture.