Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain.
Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain.
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多中心对肌萎缩性侧索硬化生物流体生物标志物的评估显示出血液神经丝轻链的至高无上。
DOI：
10.1093/braincomms/fcac029
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发表时间：
2022
影响因子：
4.8
通讯作者：
Turner MR
中科院分区：
文献类型：
--
作者：
Thompson AG;Gray E;Verber N;Bobeva Y;Lombardi V;Shepheard SR;Yildiz O;Feneberg E;Farrimond L;Dharmadasa T;Gray P;Edmond EC;Scaber J;Gagliardi D;Kirby J;Jenkins TM;Fratta P;McDermott CJ;Manohar SG;Talbot K;Malaspina A;Shaw PJ;Turner MR
在诊断患有神经退行性疾病肌萎缩侧索硬化症的患者中，疾病活动的个体化客观标志物的常规临床整合是治疗开发的关键要求。一个大型的、多中心的、基于临床的纵向队列被用于系统地评价肌萎缩侧索硬化症患者分层和潜在治疗评估中的主要候选生物流体生物标志物。招募了诊断为肌萎缩侧索硬化症（n = 258）、其他神经系统疾病（n = 80）和健康对照参与者（n = 101）的事件患者，并以3-6个月的间隔进行长达30个月的随访。检测脑脊液神经丝轻链、壳三糖苷酶1、血神经丝轻链、肌酸激酶、铁蛋白、补体C3、C4和C反应蛋白。肌萎缩侧索硬化患者血神经丝轻链、肌酸激酶、血清铁蛋白、C3和脑脊液神经丝轻链、壳三糖苷酶1均显著升高。此外，首次访视血浆神经丝轻链水平与生存率（log 10血浆神经丝轻链增加一个标准差的风险比为2.99，95%置信区间为1.65-5.41，P = 0.016）和残疾进展率密切相关，与其他预后因素无关。在报告症状发作后的前12个月内，观察到水平小幅升高（斜率为0.031 log 10单位/月，95%置信区间为0.012-0.049，P = 0.006）。将血浆神经丝轻链纳入模型作为治疗试验结果指标表明，与使用修订的肌萎缩侧索硬化功能评定量表相比，样本量显著减少，疾病减缓的早期检测是可能的。这项研究提供了强有力的证据表明，血液神经丝轻链水平优于疾病活动的常规措施在组水平。血液神经丝轻链的应用有可能从根本上减少治疗试验的持续时间和成本。它也可能为肌萎缩侧索硬化症患者提供更个性化的客观疾病活动监测目标的第一步。在一项多指标的大型多中心研究中，Thompson和Gray等人证明血浆神经丝轻链是肌萎缩侧索硬化症的主要预后生物标志物。使用临床试验建模，他们显示出其作为更快速评估候选疗法的敏感结果指标的潜力。
The routine clinical integration of individualized objective markers of disease activity in those diagnosed with the neurodegenerative disorder amyotrophic lateral sclerosis is a key requirement for therapeutic development. A large, multicentre, clinic-based, longitudinal cohort was used to systematically appraise the leading candidate biofluid biomarkers in the stratification and potential therapeutic assessment of those with amyotrophic lateral sclerosis. Incident patients diagnosed with amyotrophic lateral sclerosis (n = 258), other neurological diseases (n = 80) and healthy control participants (n = 101), were recruited and followed at intervals of 3–6 months for up to 30 months. Cerebrospinal fluid neurofilament light chain and chitotriosidase 1 and blood neurofilament light chain, creatine kinase, ferritin, complement C3 and C4 and C-reactive protein were measured. Blood neurofilament light chain, creatine kinase, serum ferritin, C3 and cerebrospinal fluid neurofilament light chain and chitotriosidase 1 were all significantly elevated in amyotrophic lateral sclerosis patients. First-visit plasma neurofilament light chain level was additionally strongly associated with survival (hazard ratio for one standard deviation increase in log10 plasma neurofilament light chain 2.99, 95% confidence interval 1.65–5.41, P = 0.016) and rate of disability progression, independent of other prognostic factors. A small increase in level was noted within the first 12 months after reported symptom onset (slope 0.031 log10 units per month, 95% confidence interval 0.012–0.049, P = 0.006). Modelling the inclusion of plasma neurofilament light chain as a therapeutic trial outcome measure demonstrated that a significant reduction in sample size and earlier detection of disease-slowing is possible, compared with using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. This study provides strong evidence that blood neurofilament light chain levels outperform conventional measures of disease activity at the group level. The application of blood neurofilament light chain has the potential to radically reduce the duration and cost of therapeutic trials. It might also offer a first step towards the goal of more personalized objective disease activity monitoring for those living with amyotrophic lateral sclerosis. In a large, multicentre study of multiple measures, Thompson and Gray et al. demonstrate plasma neurofilament light chain as the leading prognostic biomarker in amyotrophic lateral sclerosis. Using clinical trial modelling, they show its potential as a sensitive outcome measure to more rapidly assess candidate therapeutics.
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影响因子：
9.9
作者：
Lu CH;Macdonald-Wallis C;Gray E;Pearce N;Petzold A;Norgren N;Giovannoni G;Fratta P;Sidle K;Fish M;Orrell R;Howard R;Talbot K;Greensmith L;Kuhle J;Turner MR;Malaspina A
通讯作者：
Malaspina A
影响因子：
9.9
作者：
Brettschneider, J;Petzold, A;Tumani, H
通讯作者：
Tumani, H
影响因子：
9.9
作者：
Atassi, Nazem;Berry, James;Leitner, Melanie
通讯作者：
Leitner, Melanie
肌萎缩性侧硬化症患者的补体谱：一项前瞻性观察队列研究。
影响因子：
4.5
作者：
Kjældgaard AL;Pilely K;Olsen KS;Øberg Lauritsen A;Wørlich Pedersen S;Svenstrup K;Karlsborg M;Thagesen H;Blaabjerg M;Theódórsdóttir Á;Gundtoft Elmo E;Torvin Møller A;Pedersen NA;Kirkegaard N;Møller K;Garred P
通讯作者：
Garred P
DOI：
10.1056/nejmoa1916945
发表时间：
2020-09-03
期刊：
The New England journal of medicine
影响因子：
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作者：
通讯作者：
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