The impact of ethnicity on the clinical presentations of spinocerebellar ataxia type 3

Gan, Shi Rui; Figueroa, Karla P.; Xu, Hao; Perlman, Susan; Wilmot, George; Gómez, Christopher M.; Schmahmann, Jeremy D.; Paulson, Henry L.; Shakkottai, Vikram G.; Ying, Sarah H.; Zesiewicz, Theresa; Bushara, Khalaf; Geschwind, Michael D.; Xia, Guangbin; Subramony, S. H.; Rosenthal, Liana S.; Ashizawa, Tetsuo; Pulst, Stefan M.; Wang, Ning; Kuo, Sheng Han

doi:10.1016/j.parkreldis.2020.02.004

Cited by 18 publications

(20 citation statements)

References 30 publications

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“…There are hints that the size of repeats in other genes could contribute to disease, while other studies suggest that ethnicity might play a role. 49 , 50 , 51 , 52 It is also likely that genes that play a role in DNA repair also modulate disease phenotype through effects on somatic instability, as has been described for HD. 53 From a clinical trial standpoint, all these factors influencing the disease phenotype require a sufficient number of patients of each SCA subtype to be recruited to prevent confounding variables that might interfere with the interpretation of interventional studies.…”

Section: Challenges To Clinical Trialsmentioning

confidence: 99%

Spinocerebellar ataxia clinical trials: opportunities and challenges

Brooker

Edamakanti

Akasha

et al. 2021

Ann Clin Transl Neurol

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The spinocerebellar ataxias (SCAs) are a group of dominantly inherited diseases that share the defining feature of progressive cerebellar ataxia. The disease process, however, is not confined to the cerebellum; other areas of the brain, in particular, the brainstem, are also affected, resulting in a high burden of morbidity and mortality. Currently, there are no disease-modifying treatments for the SCAs, but preclinical research has led to the development of therapeutic agents ripe for testing in patients. Unfortunately, due to the rarity of these diseases and their slow and variable progression, there are substantial hurdles to overcome in conducting clinical trials. While the epidemiological features of the SCAs are immutable, the feasibility of conducting clinical trials is being addressed through a combination of strategies. These include improvements in clinical outcome measures, the identification of imaging and fluid biomarkers, and innovations in clinical trial design. In this review, we highlight current challenges in initiating clinical trials for the SCAs and also discuss pathways for researchers and clinicians to mitigate these challenges and harness opportunities for clinical trial development.

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Section: Challenges To Clinical Trialsmentioning

confidence: 99%

Spinocerebellar ataxia clinical trials: opportunities and challenges

Brooker

Edamakanti

Akasha

et al. 2021

Ann Clin Transl Neurol

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show abstract

“…We continued our literature search for Asia-specific phenotypic aspects using a citation-based search, rather than an additional broad literature search as we expected that it would result in a rather small selection of studies. Two recent studies were used as a starting point [4,5]. Other studies suggesting Asia-specific elements within a SCA subtype were reviewed and included.…”

Section: Methodsmentioning

confidence: 99%

“…Progressive ataxia is a hallmark and overlapping characteristic for all SCAs, but many SCAs are accompanied by a wide spectrum of other, non-ataxia symptoms. Previous studies have shown that this spectrum of additional symptoms depends partially on the ethnic background and geographical origin [49], resulting in SCA phenotypes with distinctive features in specific geographic locations [4]. Also, some phenotypes are associated to genotypes that occur only in very specific Asian regions (see part I).…”

Section: Part Ii: Phenotypic Differences Compared To Other Continents and Asia Specific Phenotypesmentioning

confidence: 97%

“…Recently, one study suggested the existence of a specific 'Asian' SCA3 phenotype [4], with a later age of onset and a relatively mild ataxia phenotype, compared to those with other ethnic backgrounds. However, the findings of this study have to be interpreted cautiously since there were relatively small numbers of Asian SCA3 patients in the cohort compared to patients of different ethnicity.…”

Section: Part Ii: Phenotypic Differences Compared To Other Continents and Asia Specific Phenotypesmentioning

confidence: 99%

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Spinocerebellar ataxias in Asia: Prevalence, phenotypes and management

Prooije

Norlinah

Azmin

et al. 2021

Parkinsonism & Related Disorders

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“…We also recently identified that the pathological repeat expansions of C9orf72 occur in a small subset of SCA patients, and the intermediate repeat expansions of C9orf72 can be a genetic modifier for depressive symptoms ( 22 ), further underscoring the importance of repeat interactions. Another discovery related to genetic modifiers is that ethnicity can play a role in SCA disease progression ( 23 ).…”

Section: Crc-scamentioning

confidence: 99%

Collaborative Efforts for Spinocerebellar Ataxia Research in the United States: CRC-SCA and READISCA

2020

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Spinocerebellar ataxias are progressive neurodegenerative disorders primarily affecting the cerebellum. Although the first disease-causing gene was identified nearly 30 years ago, there is no known cure to date, and only a few options exist for symptomatic treatment, with modest effects. The recently developed tools in molecular biology, such as CRISPR/Cas9 and antisense oligonucleotides, can directly act on the disease mechanisms at the genomic or RNA level in disease models. In a nutshell, we are finally just one step away from clinical trials with therapies targeting the underlying genetic cause. However, we still face the challenges for rare neurodegenerative diseases: difficulty in obtaining a large cohort size for sufficient statistical power and the need for biomarkers and clinical outcome assessments (COA) with adequate sensitivity to reflect progression or treatment responses. To overcome these obstacles, ataxia experts form research networks for clinical trial readiness. In this review, we retrace our steps of the collaborative efforts among ataxia researchers in the United States over the years to study and treat these relentless disorders and the future directions of such research networks.

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The impact of ethnicity on the clinical presentations of spinocerebellar ataxia type 3

Cited by 18 publications

References 30 publications

Spinocerebellar ataxia clinical trials: opportunities and challenges

Spinocerebellar ataxia clinical trials: opportunities and challenges

Spinocerebellar ataxias in Asia: Prevalence, phenotypes and management

Collaborative Efforts for Spinocerebellar Ataxia Research in the United States: CRC-SCA and READISCA

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