A Clinical Observational Study for Developing Disease Modifying Therapy Against Spinocerebellar Ataxia Type 31
Kinya Ishikawa1, Hanako Aoki2, Takeru Honda3, Miwa Higashi2, Tetsuya Nagata2, Takanori Yokota2
1Personalized Genomic Medicine for Health, 2Neurology, 3Center for Personalized Medicine for Healthy Aging, Tokyo Medical and Dental University
Objective:
To understand clinical progression of spinocerebellar ataxia type 31 (SCA31) through establishing clinical observational program.
Background:
Reliable fluid biomarkers and disease modifying therapies are waited for spinocerebellar ataxias (SCAs). 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). As clinical trials against SCAs using molecular therapies 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:
After collecting previously published clinical studies on various SCAs, we first tested feasibility for five years in an out-patient clinic employing SARA, 3 minutes up-and-go walking test (3mTUG) and 9 hole-peg test (9HPT), confirming a consistent progression in 14 SCA31 patients. We then designed a three-day clinical study consisting of SARA, International Cooperative Ataxia Rating Scale (ICARS), 3mTUG, 9HPT, 6 minutes walking distance, 25-foot speed walking and Kinect recordings (Front Neurol. 2020 Mar 11; 11: 179). Cerebrospinal fluid, blood and urine samples were also collected. By repeating this observation annually for each participant, we will be able to collect annual clinical progressions in all parameters.
Results:
So far, 13 participants completed first year observations. 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. By April, 2024, thirty patients are expected to be enrolled for the first year study.
Conclusions:
Our detailed clinical testing program appears generally applicable for clinical assessment and searching biomarkers in cerebellar ataxias.