Neurofilament light chain levels correlate with clinical measures in CLN3 disease.
Neurofilament light chain levels correlate with clinical measures in CLN3 disease.
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DOI：
10.1038/s41436-020-01035-3
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Porter FD
中科院分区：
文献类型：
--
作者：
Dang Do AN;Sinaii N;Masvekar RR;Baker EH;Thurm AE;Soldatos AG;Bianconi SE;Bielekova B;Porter FD
CLN 3疾病是一种在儿童期发病的神经退行性疾病。它影响不同发育阶段的多种功能。对病理生理学的不完全理解阻碍了反映疾病过程的细胞和组织生化化合物的鉴定。随着治疗方法的探索，需要更敏感，客观，可量化和临床相关的生物标志物。我们从21个CLN 3表型个体中收集了前瞻性生物样本。我们使用两种不同的测定法测量了CLN 3个体和儿科非CLN 3对照的横断面CSF和血清样本中神经丝轻链（NEFL）水平（神经元损伤的标志物）。CLN 3（CSF：2096±1202;血清：29.0±18.0 pg/mL）中的CSF和血清NEFL水平显著高于类似老化的非CLN 3（CSF：345±610;血清：6.7±3.2 pg/mL）样品。NEFL水平与统一巴顿病评定量表和适应行为综合评分以及MR波谱标记物相关。来自CSF和血清的NEFL水平强烈相关（rp=0.83; p<.0001）。CSF和血清NEFL水平在多种神经系统疾病中增加。在这里，我们表明CSF和血清NEFL水平也增加CLN 3（与非CLN 3），并与其他疾病相关的措施。这些发现表明NEFL作为CLN 3临床试验和管理中应用的相关和可行的生物标志物。
CLN3 disease is a neurodegenerative disorder with onset in childhood. It affects multiple functions at different developmental stages. Incomplete understanding of the pathophysiology hampers identification of cell and tissue biochemical compounds reflective of the disease process. As treatment approaches are being explored, more sensitive, objective, quantifiable, and clinically relevant biomarkers are needed. We collected prospective biosamples from 21 phenotyped individuals with CLN3. We measured neurofilament light chain (NEFL) levels, a marker of neuronal damage, in cross-sectional CSF and serum samples from individuals with CLN3 and in pediatric non-CLN3 controls using two different assays. CSF and serum NEFL levels are significantly higher in CLN3 (CSF: 2096±1202; serum: 29.0±18.0 pg/mL) versus similarly aged non-CLN3 (CSF: 345±610; serum: 6.7±3.2 pg/mL) samples. NEFL levels correlate with Unified Batten Disease Rating Scale and adaptive behavior composite scores, and MR spectroscopy markers. NEFL levels from CSF and serum are strongly correlated (rp=0.83; p<.0001). CSF and serum NEFL levels increase in multiple neurologic conditions. Here, we show that CSF and serum NEFL levels also increase in CLN3 (versus non-CLN3) and correlate with other disease-relevant measures. These findings suggest NEFL as a relevant and feasible biomarker for applications in CLN3 clinical trials and management.
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