D06 Influencing Huntington's disease monitoring and therapeutic development with remote quantification of blood neurofilament light protein
D06 Influencing Huntington's disease monitoring and therapeutic development with remote quantification of blood neurofilament light protein
复制标题
D06 通过血液神经丝轻蛋白的远程定量影响亨廷顿病监测和治疗开发
DOI：
10.1136/jnnp-2022-ehdn.62
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Byrne L
中科院分区：
文献类型：
--
作者：
Byrne L
背景神经丝轻蛋白（NfL）已成为疾病进展和早期发现成人型亨廷顿病（HD）的主要生物标志物候选者。青少年发病的亨廷顿氏病（JOHD）是亨廷顿氏病（HD）的一种罕见且特别具有破坏性的形式，其临床诊断具有挑战性且缺乏可靠的结果测量。目的1）评估血浆NfL作为儿童HD的生物标志物2）开发用于远程NfL定量的方法以促进频繁监测，使用在家里的手指刺血收集。MethodsWe进行了一项回顾性分析的样本和数据收集在2009年和2020年之间的Kids-HD和Kids-JHD研究。从静脉穿刺和手指针刺中采集匹配的血浆和血清。NfL浓度进行了定量使用ultrasensitive immunoassay.ResultsWe报告升高的血浆NfL浓度在JOHD和premanifest HD突变携带儿童。在预测发病20年内的儿童HD突变携带者和JOHD患者中，血浆NfL水平与尾状核和壳核体积相关。这种新的手指刺血采集方法NFL定量的初步数据显示强烈的协议与NFL水平从静脉血金standard.ConclusionsQuantifying血浆NFL浓度可能有助于临床诊断和治疗试验设计在儿科人群。远程采血可用于在家中频繁采样研究大量HD突变携带者和青少年发病HD患者的NfL。
BackgroundNeurofilament light protein (NfL) has emerged as the leading biomarker candidate for disease progression and early detection of adult-onset Huntington’s Disease (HD). Juvenile-onset Huntington’s disease (JOHD) is a rare and particularly devastating form of Huntington’s disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking.Aim1) Evaluate plasma NfL as a biomarker of HD in children 2) develop a method for remote NfL quantification to facilitate frequent monitoring, using at-home finger-prick blood collections.MethodsWe performed a retrospective analysis of samples and data collected between 2009 and 2020 from the Kids-HD and Kids-JHD studies. Matched blood plasma and serum was collected from both venipuncture and finger-prick. NfL concentrations were quantified using ultrasensitive immunoassay.ResultsWe report elevated plasma NfL concentrations in JOHD and premanifest HD mutation-carrying children. In pediatric HD mutation carriers who were within 20 years of their predicted onset and patients with JOHD, plasma NfL level was associated with caudate and putamen volumes. Preliminary data of this novel finger-prick blood collection method for NfL quantification shows strong agreement with NfL levels from the venous blood gold standard.ConclusionsQuantifying plasma NfL concentration may assist clinical diagnosis and therapeutic trial design in the pediatric population. Remote blood collection may be used to study NfL in large numbers of HD mutation carriers and Juvenile-onset HD patients at-home with frequent sampling.