Thomas Klockgether, Marcus Grobe-Einsler, Jennifer Faber
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引用次数: 0
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.
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.