RISCA : Prospective Study of Individuals at Risk for SCA1, SCA2, SCA3, SCA6, SCA7
Condition: Spinocerebellar Ataxias
MeSH terms: Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations
Study type: Observational

Summary: 
      The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of
      autosomal dominantly inherited progressive ataxia disorders. It is estimated that there are
      30,000 individuals in the European Community that directly descend from individuals affected
      by a SCA disorder and thus carry a 50% risk of having inherited an SCA mutation. These at
      risk individuals provide a unique research opportunity to prospectively study the
      presymptomatic phase of SCA disorders and to identify the earliest and most sensitive
      clinical signs and biological markers that herald the onset of the illness. This information
      is of critical importance for the development of future therapeutic interventions aimed at
      postponing the clinical onset of ataxia.

      We therefore propose to perform a prospective observational study of individuals at risk for
      the most common SCA disorders, SCA1, SCA2, SCA3 and SCA6 (RISCA). It is our aim to answer the
      following questions: (1) What is the incidence of disease manifestation in mutation carriers?
      (2) Which clinical signs precede the onset of manifest ataxia in SCA1, SCA2, SCA3 and SCA6?
      (3) What are the prevalence and incidence of preceding signs? (4) Are the prevalence and
      incidence of preceding signs affected by genotype, gender, age, estimated time until disease
      manifestation and repeat length? (5) Does the presence of certain preceding signs predict the
      manifestation of ataxia ? (6) Are there MRI alterations that precede the onset of ataxia? It
      is planned to enroll 480 study participants and to follow them at regular intervals over six
      years. At each visit, study participants are asked in a structured interview for a number of
      predefined clinical signs that potentially precede the onset of ataxia. In addition, the
      following self-assessment scales will be applied: Pittsburgh Sleep Quality Index (PSQI),
      Diagnostic Criteria for Restless Legs Syndrome, Patient´s Health Questionnaire (PHQ-9). All
      study participants will undergo a physical examination including the Scale for the Assessment
      and Rating of Ataxia (SARA). Study participants will further perform the SCA Functional
      Composite (SCA-FC) which is a comprehensive measure of functional capacity based on results
      in quantitative tests related to gait (8m timed walk), speech (PATA rate) and hand function
      (9 hole pegboard). In a subset of study participants, we will record eye movements and obtain
      volumetric MRIs. The study will also be used to collect and store blood and urine samples for
      proteomic and gene expression studies.

      RISCA is conducted by the Ataxia Study Group (ASG). It relies on the network structure
      created by the EUROSCA project.
    


Observational model: Family-Based
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        French population
      
Keywords: individuals at risk for SCA1, SCA2, SCA3, SCA6 and SCA7