NCT01934998

Parkinsonism in Spinocerebellar Ataxia Type 6

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 20 (actual)
• Sponsor: University of Chicago · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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 patients. 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 loss.

Conditions

• Spinocerebellar Ataxia Type 6

Timeline

• Start date: 2013-07-01
• Primary completion: 2015-04-01
• Completion: 2015-04-01
• First posted: 2013-09-04
• Last updated: 2015-04-28

Locations

1 site across 1 country: United States