Biomarkers in Spinocerebellar Ataxias.

IF 2.7 3区 医学 Q3 NEUROSCIENCES
Thomas Klockgether, Marcus Grobe-Einsler, Jennifer Faber
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Abstract

Biomarkers are defined as measures that indicate biological processes and responses to interventions. Spinocerebellar ataxias (SCAs) are autosomal dominantly inherited, progressive diseases. As targeted therapies for SCAs are being developed, there is a great need for biomarkers for use in clinical trials. Molecular genetic tests are firmly established as diagnostic biomarkers for SCAs. Biomarkers that monitor disease progression are needed in clinical trials that aim at slowing disease progression. Magnetic resonance imaging (MRI) volume measures and- in SCA2 - saccadic velocity are promising candidates, as they have been shown to decrease over time with larger sensitivity than clinical scales. Prognostic biomarkers indicate the likelihood of progression or a future clinical event. Potential candidates are CAG repeat length, blood neurofilament light chain (NfL) concentrations, MRI volume measures, magnetic resonance spectroscopic (MRS) metabolites, digital measures of gait variability and- in SCA2- sensory nerve amplitudes. Response biomarkers, which are capable of detecting a response to an intervention, are essential for interventional trials. In gene silencing trials, the concentrations of the proteins encoded by the targeted genes serve as response biomarkers. To date, assays for expanded ATXN3 are available. NfL has the potential to serve as a response marker across all SCA subtypes, as it is assumed to indicate ongoing neurodegeneration, but available data are yet insufficient. Although development and validation of biomarkers for SCAs are rapidly evolving, there is an urgent need for further, longitudinal, multimodal studies.

脊髓小脑共济失调的生物标志物。
生物标志物被定义为指示生物过程和对干预的反应的措施。脊髓小脑共济失调(SCAs)是常染色体显性遗传的进行性疾病。随着SCAs靶向治疗的发展,临床试验对生物标志物的需求很大。分子基因测试已牢固确立为SCAs的诊断性生物标志物。在旨在减缓疾病进展的临床试验中,需要监测疾病进展的生物标志物。磁共振成像(MRI)体积测量和(在SCA2中)跳速是有希望的候选者,因为它们已被证明随着时间的推移而降低,灵敏度高于临床尺度。预后生物标志物提示进展或未来临床事件的可能性。潜在的候选指标包括CAG重复长度、血液神经丝轻链(NfL)浓度、MRI体积测量、磁共振波谱(MRS)代谢物、步态变异性的数字测量以及(在SCA2中)感觉神经振幅。反应生物标志物,能够检测对干预的反应,是介入试验必不可少的。在基因沉默试验中,靶基因编码的蛋白浓度作为应答生物标志物。迄今为止,扩展ATXN3的检测方法是可用的。NfL有潜力作为所有SCA亚型的反应标记物,因为它被认为表明正在进行的神经退行性变,但现有数据尚不充分。尽管SCAs生物标志物的开发和验证正在迅速发展,但迫切需要进一步的纵向多模式研究。
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来源期刊
Cerebellum
Cerebellum 医学-神经科学
CiteScore
6.40
自引率
14.30%
发文量
150
审稿时长
4-8 weeks
期刊介绍: Official publication of the Society for Research on the Cerebellum devoted to genetics of cerebellar ataxias, role of cerebellum in motor control and cognitive function, and amid an ageing population, diseases associated with cerebellar dysfunction. The Cerebellum is a central source for the latest developments in fundamental neurosciences including molecular and cellular biology; behavioural neurosciences and neurochemistry; genetics; fundamental and clinical neurophysiology; neurology and neuropathology; cognition and neuroimaging. The Cerebellum benefits neuroscientists in molecular and cellular biology; neurophysiologists; researchers in neurotransmission; neurologists; radiologists; paediatricians; neuropsychologists; students of neurology and psychiatry and others.
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