Purpose

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.

Methods

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.

Results

Cerebrospinal fluid (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 magnetic resonance (MR) spectroscopy markers. NEFL levels from CSF and serum are strongly correlated (r_p = 0.83; p < 0.0001).

Conclusion

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.

中文翻译：

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神经丝轻链水平与 CLN3 疾病的临床测量相关

目的

CLN3 病是一种在儿童时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对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。

方法

我们收集了来自 21 名具有 CLN3 表型的个体的前瞻性生物样本。我们使用两种不同的测定方法测量了来自 CLN3 个体和儿科非 CLN3 对照的横截面 CSF 和血清样本中的神经丝轻链 (NEFL) 水平，这是一种神经元损伤的标志物。

结果

CLN3 (CSF: 2096 ± 1202; 血清: 29.0 ± 18.0 pg/mL) 的脑脊液 (CSF) 和血清 NEFL 水平显着高于同样年龄的非 CLN3 (CSF: 345 ± 610; 血清: 6.7 ± 3.2 pg/mL)毫升）样品。NEFL 水平与统一巴顿病评定量表和适应性行为综合评分以及磁共振 (MR) 光谱标记相关。来自 CSF 和血清的 NEFL 水平高度相关（r _p  = 0.83；p  < 0.0001）。

结论

脑脊液和血清 NEFL 水平在多种神经系统疾病中增加。在这里，我们显示 CLN3 中的 CSF 和血清 NEFL 水平也增加（与非 CLN3 相比），并与其他疾病相关措施相关。这些发现表明 NEFL 作为 CLN3 临床试验和管理中应用的相关且可行的生物标志物。