Serum neurofilament light as a biomarker in progressive multiple sclerosis.
Serum neurofilament light as a biomarker in progressive multiple sclerosis.
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DOI：
10.1212/wnl.0000000000010346
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发表时间：
2020-09-08
期刊：
影响因子：
9.9
通讯作者：
Fox RJ
中科院分区：
文献类型：
--
作者：
Kapoor R;Smith KE;Allegretta M;Arnold DL;Carroll W;Comabella M;Furlan R;Harp C;Kuhle J;Leppert D;Plavina T;Sellebjerg F;Sincock C;Teunissen CE;Topalli I;von Raison F;Walker E;Fox RJ
多发性硬化症 (MS) 治疗中对阻止进行性残疾的治疗需求尚未得到满足。如果开发出新的生物标志物来克服早期试验中揭示的传统成像结果的局限性，则可能会加速治疗的发展。 2019 年 1 月，国际进展型多发性硬化症联盟召集了一个常设专家小组，以考虑一般性多发性硬化症和特定的进展性多发性硬化症中潜在的组织液生物标志物。该小组将注意力集中在血清或血浆中的神经丝轻链 (NfL)，检查了复发性和进展性多发性硬化症的数据。在此，我们报告该小组的初步结论及其对进一步研究的建议。血清 NfL (sNfL) 是一种看似合理的神经退行性变标志物，可以准确、灵敏且可重复地测量，但应建立样本处理和分析的标准程序。复发和进展队列的研究结果一致并表明 sNfL 浓度与影像学和残疾测量相关，可以预测疾病的未来病程，并且可以预测对治疗的反应。重要的是，活动性炎症（即新的 T2 和钆增强病变）引起的疾病活动是 sNfL 的一个重要因素，因此将疾病活动与导致进行性 MS 中隐性残疾进展的疾病进展区分开来将具有挑战性。需要更多关于年龄和合并症的影响以及炎症活动和其他疾病过程的相对贡献的数据。国际进展型多发性硬化症联盟完全有能力通过联系和支持进展型多发性硬化症的相关利益相关者来推进这些举措。
There is an unmet need in multiple sclerosis (MS) therapy for treatments to stop progressive disability. The development of treatments may be accelerated if novel biomarkers are developed to overcome the limitations of traditional imaging outcomes revealed in early phase trials. In January 2019, the International Progressive MS Alliance convened a standing expert panel to consider potential tissue fluid biomarkers in MS in general and in progressive MS specifically. The panel focused their attention on neurofilament light chain (NfL) in serum or plasma, examining data from both relapsing and progressive MS. Here, we report the initial conclusions of the panel and its recommendations for further research. Serum NfL (sNfL) is a plausible marker of neurodegeneration that can be measured accurately, sensitively, and reproducibly, but standard procedures for sample processing and analysis should be established. Findings from relapsing and progressive cohorts concur and indicate that sNfL concentrations correlate with imaging and disability measures, predict the future course of the disease, and can predict response to treatment. Importantly, disease activity from active inflammation (i.e., new T2 and gadolinium-enhancing lesions) is a large contributor to sNfL, so teasing apart disease activity from the disease progression that drives insidious disability progression in progressive MS will be challenging. More data are required on the effects of age and comorbidities, as well as the relative contributions of inflammatory activity and other disease processes. The International Progressive MS Alliance is well positioned to advance these initiatives by connecting and supporting relevant stakeholders in progressive MS.