更新于：2024-11-01

Spinocerebellar Ataxia 10

脊髓小脑性共济失调10型

更新于：2024-11-01

基本信息

别名

SCA10、SCA10 Spinocerebellar Ataxia 10、SPINOCEREBELLAR ATAXIA 10

+ [7]

简介

Main features described as slowly progressive cerebellar syndrome and epilepsy, sometimes mild pyramidal signs, peripheral neuropathy and neuropsychological disturbances. Prevalence is unknown. Many kindreds have been found in Mexican and Brazilian populations. Age of onset ranges from 18 to 45 years. Caused by an ATTCT pentanucleotide repeat expansion in intron 9 of the ATXN10 gene (22q13). Exact pathogenesis has not been determined but RNA processing may be involved.

关联

项与脊髓小脑性共济失调10型相关的药物

Trigriluzole

靶点

EAAT2 x NMDA receptor x Nav1.5 x VGSCs

作用机制

EAAT2调节剂 [+3]

在研机构

Biohaven Pharmaceuticals, Inc. [+4]

原研机构

Yale University

在研适应症

马查多-约瑟夫病 [+7]

非在研适应症

阿尔茨海默症 [+5]

最高研发阶段申请上市

首次获批国家/地区-

首次获批日期1800-01-20

CAD-1883

靶点

Potassium channel

作用机制

钾离子通道激动剂

在研机构

Saniona AB

原研机构

Cadent Therapeutics, Inc.

在研适应症

特发性震颤 [+1]

非在研适应症

马查多-约瑟夫病 [+4]

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与脊髓小脑性共济失调10型相关的临床试验

NCT04301284 / Withdrawn临床2期

Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of CAD-1883 in Adults With Spinocerebellar Ataxia (Synchrony-1)

This is a randomized, double-blind, placebo-controlled Phase 2 study evaluating oral administration of CAD-1883 in the treatment of adults with a genotypic diagnosis of Spinocerebellar Ataxia (SCA). This study offers the opportunity to understand the safety, tolerability, and efficacy of CAD-1883 in the SCA patient population.

开始日期2021-06-01

申办/合作机构

Cadent Therapeutics, Inc.

NCT04495426 / Unknown statusN/AIIT

Genetic Mechanism of Conserved Ancestral Haplotype in SCA10

Spinocerebellar ataxia type 10 (SCA10) is a hereditary ataxia whose ancestral mutation occurred in East Asia. The mutation is likely to have migrated during peopling of American continents from East Asia. We found a specific rare DNA variation associated with SCA10. We test whether this variation played a key role in the birth and subsequent spreading of SCA10 mutation.

开始日期2020-09-15

申办/合作机构

The Methodist Hospital Research Institute

[+1]

NCT03701399 / Active, not recruiting临床3期

A Phase III, Long-Term, Randomized, Double-blind, Placebo-controlled Trial of Troriluzole in Adult Subjects With Spinocerebellar Ataxia.

The purpose of this study is to compare the efficacy of Troriluzole (200mg once daily) versus placebo after 48 weeks of treatment in subjects with spinocerebellar ataxia (SCA).

开始日期2019-03-08

申办/合作机构

Biohaven Pharmaceuticals, Inc.

100 项与脊髓小脑性共济失调10型相关的临床结果

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100 项与脊髓小脑性共济失调10型相关的转化医学

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0 项与脊髓小脑性共济失调10型相关的专利（医药）

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161

项与脊髓小脑性共济失调10型相关的文献（医药）

2024-11-01·Annals of Human Genetics

Spinocerebellar ataxia type 10 and Huntington disease‐like 2 in Venezuela: Further evidence of two different ancestral founder effects

Article

作者: Ikonomu, Vassiliki ; Arias, Sergio ; Paradisi, Irene

AbstractIntroductionThe American continent populations have a wide genetic diversity, as a product of the admixture of three ethnic groups: Amerindian, European, and African Sub‐Saharan. Spinocerebellar ataxia type 10 (SCA10) and Huntington disease‐like 2 (HDL2) have very ancient ancestral origins but are restricted to two populations: Amerindian and African Sub‐Saharan, respectively. This study aimed to investigate the genetic epidemiological features of these diseases in Venezuela.MethodsIn‐phase haplotypes with the expanded alleles were established in seven unrelated index cases diagnosed with SCA10 and in 11 unrelated index cases diagnosed with HDL2. The origins of remote ancestors were recorded.ResultsThe geographic origin of the ancestors showed grouping in clusters. SCA10 had a minimal general prevalence of 1:256,174 families in the country, but within the identified geographic clusters, the prevalence ranged from 5 per 100,000 to 43 per 100,000 families. HDL2 had a general prevalence of 1:163,016 families, however, within the clusters, the prevalence ranged from 31 per 100,000 to 60 per 100,000 families. The locus‐specific haplotype shared by all families worldwide, including the Venezuelans, supports a single old ancestral origin in each case.ConclusionKnowing the genetic ancestry and geographic origins of patients in Ibero‐American mixed populations could have significant diagnostic implications; thus, both diseases in Venezuela should always be first explored in patients with a suggestive phenotype and ancestors coming from the same known geographic clusters.

2024-09-03·Human Molecular Genetics

Extended haplotype with rs41524547-G defines the ancestral origin of SCA10

Article

作者: Skov, Laurits ; Yabe, Ichiro ; Johnson, Kristy L ; Hashem, Vera ; Zhang, Linwei ; Gan, Shi Rui ; Vincent, Justin ; Arredondo, Maria J ; McFarland, Karen N ; Zeng, Desmond ; Ashizawa, Tetsuo ; Rasmussen, Astrid ; Tiwari, Anjana

AbstractSpinocerebellar ataxia type 10 (SCA10) is a rare autosomal dominant ataxia caused by a large expansion of the (ATTCT)n repeat in ATXN10. SCA10 was described in Native American and Asian individuals which prompted a search for an expanded haplotype to confirm a common ancestral origin for the expansion event. All patients with SCA10 expansions in our cohort share a single haplotype defined at the 5′-end by the minor allele of rs41524547, located ~35 kb upstream of the SCA10 expansion. Intriguingly, rs41524547 is located within the miRNA gene, MIR4762, within its DROSHA cleavage site and just outside the seed sequence for mir4792-5p. The world-wide frequency of rs41524547-G is less than 5% and found almost exclusively in the Americas and East Asia—a geographic distribution that mirrors reported SCA10 cases. We identified rs41524547-G(+) DNA from the 1000 Genomes/International Genome Sample Resource and our own general population samples and identified SCA10 repeat expansions in up to 25% of these samples. The reduced penetrance of these SCA10 expansions may be explained by a young (pre-onset) age at sample collection, a small repeat size, purity of repeat units, or the disruption of miR4762-5p function. We conclude that rs41524547-G is the most robust at-risk SNP allele for SCA10, is useful for screening of SCA10 expansions in population genetics studies and provides the most compelling evidence to date for a single, prehistoric origin of SCA10 expansions sometime prior to or during the migration of individuals across the Bering Land Bridge into the Americas.

2024-03-01·Neurological Sciences

Autosomal recessive spino-cerebellar ataxia type 10 (SCAR10): clinical presentation associated with c.289delA ANO10 gene variant

Letter

作者: Alonge, Paolo ; Grillo, Lucia ; Lupica, Antonino ; Calì, Francesco ; Norata, Davide ; Sturnio, Maurizio ; Brighina, Filippo ; Di Stefano, Vincenzo ; Costa, Vanessa