Padilla Cameron J, Alexander Derek M, Labor Desiree A, Albert Orsolya K, Robbins Kendall P, Berry-Kravis Elizabeth, Porter Forbes D
Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA.
Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA.
Am J Med Genet A. 2025 May;197(5):e63970. doi: 10.1002/ajmg.a.63970. Epub 2024 Dec 17.
Niemann-Pick disease, type C1 (NPC1) is an ultra rare, autosomal recessive disorder characterized by impaired intracellular cholesterol trafficking. This study assessed neuron-specific enolase (NSE) as a biomarker for disease status and treatment response in individuals with NPC1. We also evaluated the concordance between serum and cerebrospinal fluid (CSF) NSE measurements. A total of 34 individuals with NPC1 were included in this analysis. Overall, 10 participants were used to compare concurrent samples of CSF and serum NSE. NSE levels were correlated with indexes of disease severity (Annual Severity Increment Score [ASIS] and age of neurological onset) and disease burden (NPC Neurological Severity Score [NSS]). NSE was elevated in CSF, but paired CSF/serum samples were not correlated (r = -0.16, p = 0.64). Additionally, no significant correlations were observed between serum NSE levels and clinical measures of either disease burden or severity. CSF NSE values showed a significant positive association with the ASIS (r = 0.37, p = 0.0291) but no association with age of neurological onset or NPC NSSs. Longitudinal analysis of nine participants showed a significant (p = 0.0317) decrease in CSF NSE levels after initiation of intrathecal 2-hydroxypropyl-β-cyclodextrin (IT HPβCD) therapy. This study suggests that CSF NSE may have some utility as a biomarker in NPC1 therapeutic trials.
1型尼曼-匹克病（NPC1）是一种极为罕见的常染色体隐性疾病，其特征为细胞内胆固醇转运受损。本研究评估了神经元特异性烯醇化酶（NSE）作为NPC1患者疾病状态和治疗反应生物标志物的情况。我们还评估了血清和脑脊液（CSF）中NSE测量值之间的一致性。本分析共纳入了34例NPC1患者。总体而言，10名参与者用于比较CSF和血清NSE的同步样本。NSE水平与疾病严重程度指标（年度严重程度增量评分[ASIS]和神经发病年龄）以及疾病负担（NPC神经严重程度评分[NSS]）相关。CSF中NSE升高，但配对的CSF/血清样本不相关（r = -0.16，p = 0.64）。此外，血清NSE水平与疾病负担或严重程度的临床指标之间未观察到显著相关性。CSF NSE值与ASIS呈显著正相关（r = 0.37，p = 0.0291），但与神经发病年龄或NPC NSS无关。对9名参与者的纵向分析显示，鞘内注射2-羟丙基-β-环糊精（IT HPβCD）治疗开始后，CSF NSE水平显著下降（p = 0.0317）。本研究表明，CSF NSE可能作为NPC1治疗试验中的生物标志物具有一定作用。
