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. 2024 Aug 22;50(1):154.
doi: 10.1186/s13052-024-01726-6.

Dysregulation of cerebrospinal fluid metabolism profiles in spinal muscular atrophy patients: a case control study

Wei Zhuang #  1 , Minying Wang #  2 , Mei Lu #  2 , Zhehui Chen  2 , Meifen Luo  2 , Wanlong Lin  3 , Xudong Wang  4
Affiliations

Dysregulation of cerebrospinal fluid metabolism profiles in spinal muscular atrophy patients: a case control study

Wei Zhuang et al. Ital J Pediatr. .

Abstract

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.

Keywords: Cerebrospinal fluid; Metabolic disorder; Metabolomics; N-acetylneuraminic acid; Spinal muscular atrophy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
OPLS-DA models to separate patients with SMA from controls. A OPLS-DA plot for the positive ion model; B OPLS-DA plot for the negative ion model
Fig. 2
Fig. 2
Changes of major metabolites in cerebrospinal fluid samples from SMA group and control group. A The fold change, VIP and P value of differentially abundant metabolites; B Heatmap clustering of differentially abundant metabolites in SMA group and control group; C Differences in metabolic material charge ratio and P value scatter plot
Fig. 3
Fig. 3
Differentially abundant metabolites in cerebrospinal fluid samples from the SMA group and the control group
Fig. 4
Fig. 4
Pathway analysis of differentially abundant metabolites. A Histogram of top five pathways. The comparison between the control group and the SMA group showed the most significant changes in amino acid and lipid metabolism pathway; B Bubble diagram of pathways; C Network diagram
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