A Longitudinal Observational Study for Assessing Clinical Markers in Spinocerebellar Ataxia Type 31
Objective:
To understand clinical progression of spinocerebellar ataxia type 31 (SCA31) through establishing clinical observational program.
Background:
Spinocerebellar ataxia type 31 (SCA31) is characterized by a late-onset slowly progressive cerebellar ataxia, caused by a penta-nucleotide expansion containing (TGGAA)n in an intron of BEAN1 (Am J Hum Genet 2009; 85: 544-57). This disease is common SCA in Japanese, while it is not found in other ethnicity. As clinical trials against SCAs are expected in future, it became essential for us to understand progression rates as well as biomarkers in SCA31. Previous studies reported that an annual progression rate of SCA31 in the Scale for the Assessment and Rating of Ataxia (SARA) score was 0.8 ± 0.1 points (Cerebellum 2017; 16: 518-24). However, detailed clinical parameters are needed to address efficacies of therapies.
Design/Methods:
We designed a three-day clinical study consisting of SARA, International Cooperative Ataxia Rating Scale (ICARS), 6 minutes-walk (6MW), 10 meter walking speed (10mWS), 25-foot speed walking (25FWS) and 9HPT. Cerebrospinal fluid, blood and urine samples were also collected. By repeating this observation every 48 weeks in each participant, we will be able to collect annual clinical progressions in all parameters.
Results:
Twenty-two participants completed first year and 48 weeks observations, allowing us to measure clinical changes in the 48 weeks. SARA score worsened 0.88 point in the 48weeks, and two out of three walking parameters (10mWS and 25FWS) were found to show clinical worsening in the 48 weeks period (Wilcoxon signed rank exact test; p=0.0275～0.000586). Despite that our program is more comprehensive than other programs such as Ataxia Functional Composite Scale (Mov Disord 2021;36(2):283-297), no significant concerns were encountered.
Conclusions:
We are considering to use these parameters in our first-in-human clinical trial in SCA31, which we expect to launch in FY 2029.
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