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Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis

肌萎缩侧索硬化 临床试验 生物标志物 疾病 医学 生物标志物发现 肿瘤科 生物信息学 精密医学 病理 内科学 生物 蛋白质组学 生物化学 基因
作者
Marie Dreger,Robert Steinbach,Markus Otto,Martin R. Turner,Julian Großkreutz
出处
期刊:Journal of Neurology, Neurosurgery, and Psychiatry [BMJ]
卷期号:93 (4): 422-435 被引量:28
标识
DOI:10.1136/jnnp-2021-327503
摘要

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease, and only modest disease-modifying strategies have been established to date. Numerous clinical trials have been conducted in the past years, but have been severely hampered by the wide-ranging heterogeneity of both the biological origins and clinical characteristics of the disease. Thus, reliable biomarkers of disease activity are urgently needed to stratify patients into homogenous groups with aligned disease trajectories to allow a more effective design of clinical trial. In this review, the most promising candidate biomarkers in the cerebrospinal fluid (CSF) of patients with ALS will be summarised. Correlations between biomarker levels and clinical outcome parameters are discussed, while highlighting potential pitfalls and intercorrelations of these clinical parameters. Several CSF molecules have shown potential as biomarkers of progression and prognosis, but large, international, multicentric and longitudinal studies are crucial for validation. A more standardised choice of clinical endpoints in these studies, as well as the application of individualised models of clinical progression, would allow the quantification of disease trajectories, thereby allowing a more accurate analysis of the clinical implications of candidate biomarkers. Additionally, a comparative analysis of several biomarkers and ideally the application of a multivariate analysis including comprehensive genotypic, phenotypic and clinical characteristics collectively contributing to biomarker levels in the CSF, could promote their verification. Thus, reliable prognostic markers and markers of disease activity may improve clinical trial design and patient management in the direction of precision medicine.
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