Integrated Functional Evaluation of the Cerebellum

Spinocerebellar ataxias (SCAs) are autosomal dominantly inherited neurological disorders, characterized by a predominant atrophy of the cerebellum and the brainstem. The most common forms are caused by abnormal CAG repeat expansions, encoding elongated polyglutamine (polyQ).

Nowadays, no preventive or curative treatments are available but different therapeutic approaches are ongoing. Antisense oligonucleotides (ASOs) therapy showed promising results in Huntington disease (HD), a disease that shares with the SCAs the same mutational mechanism. ASOs are currently under development for SCAs.

However, in SCAs, clinical scales as an only criteria to monitor a treatment are not appropriate because of the lack of sensitivity of change and the small number of patients available. The importance to dispose of outcome measures to inform about the efficacy of a treatment is fundamental as well as of new alternative designs to conduct a clinical trial in rare diseases with small sample sizes.

A comprehensive, multimodal approach is hence needed to provide a translational and integrated overview of cerebellar dysfunction in polyQ SCAs over a year.

Common inclusion criteria for all participants:

• Ability to walk independently 30 foot without an assistive device
• Able to stand unassisted for 30 seconds
• Affiliated with the French social security, or a social security equivalent, if they are not French.
• Capacity to consent
• Signed Informed Consent by the subject
• Ability to undergo MRI scanning

Inclusion criteria

for SCA patients:

• Genetic diagnosis of SCA 2 or 7 (available CAG repeat length)
• SARA score ≤15

Inclusion criteria

for control participants:

• Negative Genetic diagnosis of SCA2/SCA7 available
• No significant neurological symptoms
• SARA score < 5

Common inclusion criteria for elective participant for CSF sampling:

• Ability to undergo a lumbar puncture

Exclusion criteria

• Subjects currently receiving, or having received within 2 months prior to enrolment into this study, any investigational drug
• Pregnancy or breastfeeding
• Genotype consistent with other inherited ataxias
• Changes in coordinative physical and occupational therapy for ataxia 2 months prior to study participation
• Concomitant disorder(s) or condition(s) that affects assessment of ataxia or severity of ataxia during this study
• Contra-indications to MRI examination
• Person deprived of their liberty by judicial or administrative decision