Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Zandl-Lang, M; Züllig, T; Holzer, M; Eichmann, TO; Darnhofer, B; Schwerin-Nagel, A; Zobel, J; Haidl, H; Biebl, A; Köfeler, H; Plecko, B.
Multi-omics profiling in spinal muscular atrophy (SMA): investigating lipid and metabolic alterations through longitudinal CSF analysis of Nusinersen-treated patients.
J Neurol. 2025; 272(3): 183
Doi: 10.1007/s00415-025-12909-4
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- Leading authors Med Uni Graz
- Zandl-Lang Martina
- Co-authors Med Uni Graz
- Darnhofer Barbara
- Eichmann Thomas
- Haidl Harald
- Holzer Michael
- Köfeler Harald
- Plecko Barbara
- Schwerin-Nagel Anette
- Zobel Joachim
- Züllig Thomas
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- Abstract:
- Spinal muscular atrophy (SMA) is a rare neuromuscular disease caused by biallelic mutations in the SMN1 gene, leading to progressive muscle weakness due to degeneration of the anterior horn cells. Since 2017, SMA patients can be treated with the anti-sense oligonucleotide Nusinersen, which promotes alternative splicing of the SMN2 gene, by regular intrathecal injections. In this prospective study, we applied metabolomic, lipidomic, and proteomic analysis to examine sequential CSF samples from 13 SMA patients and controls. This multi-omic approach identified over 800 proteins and 400 small molecules including lipids. Multivariate analysis of multi-omic data successfully discriminated between the CSF derived from SMA patients and control subjects. Lipidomic analysis revealed increased levels of cholesteryl esters and lyso-phospholipids, along with reduced levels of cholesterol and phospholipids in the CSF of SMA patients as compared to healthy controls. These data, combined with results from functional assays, led us to conclude that SMA patients exhibit altered levels and function of high-density-lipoprotein (HDL)-like particles in the CSF. Notably, Nusinersen therapy was observed to reverse disease-specific profile changes toward a physiological state, potentially explicable by restoring HDL function.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Oligonucleotides - pharmacology
- Male - administration & dosage
- Female - administration & dosage
- Muscular Atrophy, Spinal - drug therapy, cerebrospinal fluid
- Child, Preschool - administration & dosage
- Child - administration & dosage
- Longitudinal Studies - administration & dosage
- Proteomics - administration & dosage
- Lipidomics - administration & dosage
- Prospective Studies - administration & dosage
- Adolescent - administration & dosage
- Infant - administration & dosage
- Adult - administration & dosage
- Lipid Metabolism - drug effects
- Multiomics - administration & dosage
- Find related publications in this database (Keywords)
- Mass spectrometry
- Biomarker
- Omics
- Lipid metabolism
- Neuromuscular