背景:脊髓性肌萎缩症(SMA)是一种神经退行性疾病。尽管先前的研究已经在各种情况下调查了SMA的代谢组,与健康对照相比,脑脊液(CSF)代谢组学研究存在差距.CSF代谢组学可以提供对中枢神经系统功能和患者预后的见解。本研究旨在调查未经治疗的SMA患者的CSF代谢谱,以增强我们对SMA代谢失调的理解。
方法:本病例对照研究包括15名SMA患者和14名对照受试者。收集脑脊液样本,并进行非靶向代谢组学检测SMA和对照组的代谢产物。
结果:SMA组和对照组之间共有118种代谢物丰度发生显著变化。其中,确定了27种对投影(VIP)≥1.5具有不同重要性的代谢物。前5位差异代谢产物为N-乙酰神经氨酸(VIP=2.38,倍数变化=0.43,P=5.49×10-5),2,3-二羟基吲哚(VIP=2.33,倍数变化=0.39,P=1.81×10-4),lumichrome(VIP=2.30,倍数变化=0.48,P=7.90×10-5),花生酸(VIP=2.23,倍数变化=10.79,P=6.50×10-6),和10-羟基癸酸(VIP=2.23,倍数变化=0.60,P=1.44×10-4)。聚类分析表明,差异代谢物主要聚集在两个主要类别:蛋白质和氨基酸代谢,和脂质代谢。
结论:研究结果突出了SMA的复杂性,对多种代谢途径有广泛的影响,特别是在氨基酸和脂质代谢中。N-乙酰神经氨酸可能是SMA功能改善的潜在治疗方法。与SMA代谢失调相关的确切机制和潜在治疗靶点需要进一步研究。
BACKGROUND: Spinal muscular atrophy (SMA) is a neurodegenerative disorder. Although prior studies have investigated the metabolomes of SMA in various contexts, there is a gap in research on cerebrospinal fluid (CSF) metabolomics compared to healthy controls. CSF metabolomics can provide insights into central nervous system function and patient outcomes. This study aims to investigate CSF metabolite profiles in untreated SMA patients to enhance our understanding of SMA metabolic dysregulation.
METHODS: This case control study included 15 SMA patients and 14 control subjects. CSF samples were collected, and untargeted metabolomics was conducted to detect metabolites in SMA and control groups.
RESULTS: A total of 118 metabolites abundance were significantly changed between the SMA and control groups. Of those, 27 metabolites with variable importance for the projection (VIP) ≥ 1.5 were identified. The top 5 differential metabolites were N-acetylneuraminic acid (VIP = 2.38, Fold change = 0.43, P = 5.49 × 10-5), 2,3-dihydroxyindole (VIP = 2.33, Fold change = 0.39, P = 1.81 × 10-4), lumichrome (VIP = 2.30, Fold change = 0.48, P = 7.90 × 10-5), arachidic acid (VIP = 2.23, Fold change = 10.79, P = 6.50 × 10-6), and 10-hydroxydecanoic acid (VIP = 2.23, Fold change = 0.60, P = 1.44 × 10-4). Cluster analysis demonstrated that the differentially metabolites predominantly clustered within two main categories: protein and amino acid metabolism, and lipid metabolism.
CONCLUSIONS: The findings highlight the complexity of SMA, with widespread effects on multiple metabolic pathways, particularly in amino acid and lipid metabolism. N-acetylneuraminic acid may be a potential treatment for functional improvement in SMA. The exact mechanisms and potential therapeutic targets associated with metabolic dysregulation in SMA require further investigation.