ArticleEBioMedicine2023
A pentasaccharide for monitoring pharmacodynamic response to gene therapy in GM1 gangliosidosis.
Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- AAV9 Gene Therapy in Type II GM1 Gangliosidosis - A Phase 1-2 Trial.The New England journal of medicine · 2026Trial
- Expanded Access use of Intravenous Gene Transfer with AAV9-GLB1 in a Juvenile GM1 Gangliosidosis Participant.medRxiv : the preprint server for health sciences · 2026Article
- Diagnostic and therapeutic applications of the glycan biomarker H3N2b in GM1 Gangliosidosis.Molecular genetics and metabolism · 2026Article
- Article
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Mechanistic elucidation of Wuling Powder targeting macrophage polarization to ameliorate renal ischemia-reperfusion injury via multidimensional computational systems pharmacology coupled with experimental validation.Frontiers in pharmacology · 2026Article
- Secondary accumulation of lyso-platelet activating factors in lysosomal storage diseases.Molecular genetics and metabolism · 2025Article
- Application of Chelex-100 and SPR-IDA Resin in Combination with the Optimized Beam Deflection Spectrometry for High-Sensitivity Determination of Iron Species in Sediment Porewater.Sensors (Basel, Switzerland) · 2025Article
- SMQVP: A Web Application for Spatial Metabolomics Quality Visualization and Processing.Metabolites · 2025Article
- Metabolic Reprogramming in HIV+ CD4Metabolites · 2025Article
- Purine Metabolism Pathway Influence on Running Capacity in Rats.Metabolites · 2025Article
- Retrospective assessment of clinical global impression of severity and change in GM1 gangliosidosis: a tool to score natural history data in rare disease cohorts.Orphanet journal of rare diseases · 2025Article
- Challenges in Lipidomics Biomarker Identification: Avoiding the Pitfalls and Improving Reproducibility.Metabolites · 2024Article
- Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Analysis of Urinary Oligosaccharides and Glycoamino Acids for the Diagnosis of Mucopolysaccharidosis and Glycoproteinosis.Clinical chemistry · 2024Article
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundGM1 gangliosidosis is a rare, fatal, neurodegenerative disease caused by mutations in the GLB1 gene and deficiency in β-galactosidase. Delay of symptom onset and increase in lifespan in a GM1 gangliosidosis cat model after adeno-associated viral (AAV) gene therapy treatment provide the basis for AAV gene therapy trials. The availability of validated biomarkers would greatly improve assessment of therapeutic efficacy.
methodsThe liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to screen oligosaccharides as potential biomarkers for GM1 gangliosidosis. The structures of pentasaccharide biomarkers were determined with mass spectrometry, as well as chemical and enzymatic degradations. Comparison of LC-MS/MS data of endogenous and synthetic compounds confirmed the identification. The study samples were analyzed with fully validated LC-MS/MS methods.
findingsWe identified two pentasaccharide biomarkers, H3N2a and H3N2b, that were elevated more than 18-fold in patient plasma, cerebrospinal fluid (CSF), and urine. Only H3N2b was detectable in the cat model, and it was negatively correlated with β-galactosidase activity. Following intravenous (IV) AAV9 gene therapy treatment, reduction of H3N2b was observed in central nervous system, urine, plasma, and CSF samples from the cat model and in urine, plasma, and CSF samples from a patient. Reduction of H3N2b accurately reflected normalization of neuropathology in the cat model and improvement of clinical outcomes in the patient. INTERPRETATIONS: These results demonstrate that H3N2b is a useful pharmacodynamic biomarker to evaluate the efficacy of gene therapy for GM1 gangliosidosis. H3N2b will facilitate the translation of gene therapy from animal models to patients.
fundingThis work was supported by grants U01NS114156, R01HD060576, ZIAHG200409, and P30 DK020579 from the National Institutes of Health (NIH) and a grant from National Tay-Sachs and Allied Diseases Association Inc.
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