Parkinsonism in Spinocerebellar Ataxia Type 6

Brief Title

Parkinsonism in Spinocerebellar Ataxia Type 6

Official Title

Characterization of the Parkinsonism and Other Non-ataxia Spectrum and Striatal Dopaminergic Degeneration in Spinocerebellar Ataxia Type 6

Brief Summary

      The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of dominantly
      inherited progressive ataxia disorders. More than 30 different gene loci have been identified
      so far. The most common SCAs, which together account for more than half of all affected
      families, are SCA1, SCA2, SCA3, and SCA6. Each of these disorders is caused by a translated
      CAG repeat expansion mutation. SCA1, SCA2, and SCA3 usually have an onset between 30 and 40,
      and SCA6 usually begins at the age of 50 to 60. In addition to progressive ataxia, SCA1,
      SCA2, and SCA3 frequently present with additional non-ataxic symptoms, including
      parkinsonism. Carbidopa/levodopa was found to have a good therapeutic effect on parkinsonism.

      The SCA6 used to be considered a pure cerebellar disorder. However, a recent large study on
      natural history of SCAs found that patients with SCA6 often had nonataxia symptoms, an
      observation that challenges the view that SCA6 is a purely cerebellar disorder. Parkinsonism
      in SCA6 was rarely reported, except in a case serial, or a small size study in Korean

      Dopamine transporter (DAT) is a very reliable dopaminergic neuronal marker. Reduction in DAT
      density detected by I123 SPECT DaTscanTM in the dopaminergic neuron terminal striatum was
      reported in one small size study consisting of eight SCA6 patients in Korea. There was also a
      PET study using different radioligand for DAT in a small group of SCA6 patients in Germany,
      which found sub-clinical change in DAT density in some patients with SCA6.

      There has been no study so far in the US on parkinsonism and other non-ataxia spectrum and
      striatal dopaminergic damage in SCA6, probably because non-ataxia feature of SCA6 hasn't
      received much attention, and also because DaTscanTM hasn't been clinically available in US
      until recently. The only two published studies on SCA6 and DAT were from Korea and Germany,
      which were of small subject size. There has been no treatment available for SCA6 so far.

      Our hypothesis is that parkinsonism and other non-ataxia spectrum and striatal dopaminergic
      neurodegeneration are part of the SCA6 disease spectrum.

Detailed Description

      Specifically, we would expect to see

        1. Parkinsonism and other non-ataxia symptoms are more commonly present in SCA6 patients
           than we used to think.

        2. Parkinsonism is associated with the loss of DAT in striatum.

        3. Parkinsonism and other non-ataxia symptoms are also associated with the expanded allele
           repeat number, the disease duration, and the severity of ataxia, in addition to DAT

Study Type


Primary Outcome

The primary outcome would be the clinical feature of the parkinsonism and change in DAT density in putamen and caudate

Secondary Outcome

 The secondary outcome would be the INAS score


Spinocerebellar Ataxia Type 6

Study Arms / Comparison Groups

 SCA6 and control
Description:  SCA6 and control


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

July 2013

Completion Date

April 2015

Primary Completion Date

April 2015

Eligibility Criteria

        Inclusion Criteria:

          -  Patients 18 years old or older with progressive ataxia and positive genetic test for
             SCA6 will be recruited. Those who take medications known to affect DAT binding, such
             as Ritalin, Cocaine, and Adderall will be excluded. Those taking SSRIs for depression
             will be asked to stop the medications for at least 24 hours before the DaTscanTM. All
             study patients will have the decision making capability to understand the study and
             requirements and consent for themselves.

        The age-matched controls will most likely be the patients' spouses. However friends or
        family members may also serve as controls if needed. Control subjects will have no ataxia,
        parkinsonism, myoclonus and other focal neurological symptoms and deficits.

        Exclusion Criteria:

          -  Subjects who don't meet the inclusion criteria.




18 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers


Tao Xie, MD PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

University of Chicago

Study Sponsor

Tao Xie, MD PhD, Principal Investigator, University of Chicago

Verification Date

April 2015