Biofluid Biomarkers in Parkinson's Disease: Clarity Amid Controversy.
Biofluid Biomarkers in Parkinson's Disease: Clarity Amid Controversy.
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帕金森病的生物流体生物标志物：争议中的清晰度。
DOI：
10.1002/mds.28030
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Vieira SRL
中科院分区：
文献类型：
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作者：
Vieira SRL
目前迫切需要开发帕金森病（PD）的生物标志物。经过验证的生物标志物促进了个性化医疗的发展，有望提高诊断准确性、疾病监测、患者分层和客观衡量治疗反应。PD生物标志物的缺乏限制了有希望的临床前疾病改善疗法的临床转化。事实上，仅仅依赖临床评估和评定量表作为结果衡量标准可能是最近isradipine和肌苷3期研究失败的原因之一。这些措施经常与对症治疗相混淆，无法反映疾病状态的细微但重要的变化，这些变化可能反映疾病进展的改变。此外，考虑到帕金森病的临床异质性，生物标志物的另一个目标集中在临床试验中招募的患者群体的分层和丰富。测试定义明确的疾病亚组，取代传统的大型和异质性患者队列，可以提高临床试验的疗效。此外，识别和随后纳入无症状PD风险个体进入神经保护药物试验仍然是生物标志物开发的重要目标。PD生物流体生物标志物的发现领域，以前充满了令人失望和不一致的结果，最近聚集了显著的势头。旨在产生强大生物标志物的指南建议转向纵向、大规模的合作研究和所采用方法的标准化。此外，新兴的有前景的生物标志物随后应经过广泛的验证过程。临床有用的生物标志物必须满足以下标准：合理的效应大小（即曲线下面积，AUC为0.8）；疾病和对照受试者之间的数值重叠最小的可重复性；易于量化，不受其他合并症的影响。在技术进步和易于获取样本的驱动下，识别PD中基于生物流体的生物标志物（特别是血液和脑脊液[CSF]）已经取代传统的神经影像学成为研究焦点。虽然没有这样的生物标志物符合上述临床应用标准，但本观点将总结在PD中寻找生物流体生物标志物的有希望的发现，强调关键挑战，并为未来的方向提出建议。
A critical need exists to develop biomarkers for Parkinson’s disease (PD). Facilitating the evolution toward personalized medicine, validated biomarkers hold the promise of improved diagnostic accuracy, disease monitoring, patient stratification, and objectively measuring treatment responses. The lack of biomarkers for PD has limited the clinical translation of promising preclinical disease-modifying therapies. Indeed, sole reliance on clinical assessments and rating scales as outcome measures may have contributed to the recent failure of isradipine and inosine phase 3 studies. 1 Such measures are frequently confounded by symptomatic treatment and unable to reflect subtle but important changes in the disease state that may reflect modification of disease progression. Moreover, given the welldescribed clinical heterogeneity of PD, another goal of biomarkers centers on the stratification and enrichment of patient populations recruited into clinical trials. Testing well-defined disease subgroups, in place of the traditional large and heterogenous patient cohorts, could improve clinical trial efficacy. 2 Furthermore, the identification and subsequent enrollment of asymptomatic individuals at risk for PD into neuroprotective drug trials remains an important goal for biomarker development.The PD biofluid biomarker discovery field, previously fraught with disappointing and inconsistent results, has recently gathered significant momentum. Guidelines aiming to generate robust biomarkers recommend a shift toward longitudinal, large-scale collaborative studies and standardization of methods employed. 2 Furthermore, emerging promising biomarkers should subsequently be subjected to an extensive validation process. Clinically useful biomarkers must fulfill the following criteria, listed as: a reasonable effect size (ie, area under the curve, AUC> 0.8); reproducibility with minimal overlap in values between disease and control subjects; easily quantifiable and unaffected by other comorbidities. 2 Driven by technological advances and ease of sample accessibility, identifying biofluid-based biomarkers in PD (particularly, in blood and cerebrospinal fuid [CSF]) has overtaken traditional neuroimaging as a research focal point. 3 Although no such biomarkers meet the aforementioned criteria for clinical utility, this Viewpoint will summarize promising findings in the search for biofluid biomarkers in PD, highlighting key challenges and setting out recommendations for future directions.