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Relative distribution of Gb3 isoforms/analogs in NOD/SCID/Fabry mice tissues determined by tandem mass spectrometry
Philippe Provençal1, Michel Boutin1, Shaalee Dworski2
1Department of Pediatrics, Division of Medical Genetics, Faculty of Medicine & Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4 Canada.
Aim:
Fabry disease is a lysosomal storage disorder leading to glycosphingolipid accumulation in different organs, tissues and biological fluids. The development of a Fabry disease gene therapy trial is underway in Canada. A tool to determine the distribution of Gb3 biomarkers in tissues of Fabry mice might be applicable to monitor the effect of gene therapy. Results & methodology: An ultra-performance LC-MS/MS (UPLC-MS/MS) method for the analysis of 22 Gb3 isoform/analogs in various Fabry mice tissues was developed and validated. Marked variation in biomarker organ distribution was found with higher levels in the spleen, followed by the small intestine, kidneys, lungs, heart, liver and brain.
Conclusion:
The devised method is sensitive and useful for the evaluation of biomarker profiles in Fabry mice.
Insights
A new ultra-performance LC-MS/MS method accurately measures globotriaosylceramide (Gb3) biomarkers in Fabry disease mouse tissues. This tool aids in monitoring gene therapy effectiveness by revealing varied Gb3 distribution across organs.
Area of Science:
- Biochemistry
- Genetics
- Pharmacology
Background:
- Fabry disease is a lysosomal storage disorder characterized by glycosphingolipid accumulation.
- Gene therapy for Fabry disease is under development, necessitating tools for monitoring treatment efficacy.
- Understanding biomarker distribution is crucial for assessing therapeutic outcomes.
Purpose of the Study:
- To develop and validate an ultra-performance LC-MS/MS method for quantifying Gb3 isoforms and analogs in Fabry mouse tissues.
- To determine the organ-specific distribution of Gb3 biomarkers in a mouse model of Fabry disease.
Main Methods:
- Ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was employed.
- The method was validated for the analysis of 22 Gb3 isoform/analogs.
- Analysis was performed on various tissues from Fabry mice.
Main Results:
- A sensitive UPLC-MS/MS method for Gb3 biomarker analysis was successfully developed and validated.
- Significant variations in biomarker organ distribution were observed.
- Higher Gb3 levels were detected in the spleen, followed by the small intestine, kidneys, lungs, heart, liver, and brain.
Conclusions:
- The developed UPLC-MS/MS method is sensitive and effective for evaluating biomarker profiles in Fabry mice.
- This tool can potentially be used to monitor the effects of gene therapy for Fabry disease.
