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Background <p>Gaucher disease (GD) is a common lysosomal storage disorder caused by mutations in the glucocerebrosidase-1 (GBA1) gene, resulting in the deficiency of the lysosomal enzyme β-glucocerebrosidase (GCase) and the subsequent accumulation of glucosylceramide (GluCer) and glucosylsphingosine (GlcSph; Lyso-Gb1). However, major gaps remain regarding the management of neurological symptoms and the validation of effective biomarkers.</p> Objective <p>This review summarizes current insights from preclinical models and omics-based approaches to understand GD pathophysiology, biomarker discovery, and emerging therapeutic strategies.</p> Methods <p>A comprehensive literature review was performed focusing on preclinical models (mouse, zebrafish, Drosophila, medaka, canine, and ovine) and omics technologies, including proteomics, genomics, and metabolomics. Relevant studies on biomarkers and therapies were critically analysed.</p> Results <p>The preclinical model has shed light on several important pathogenic mechanisms, including lipid accumulation, immune dysfunction, and neuroinflammation. There have been advances in the treatment of GD using enzyme replacement therapy (ERT) and substrate reduction therapy (SRT), but these are limited by their high cost, lack of accessibility, and lack of effectiveness against the neuronopathic variants. Different biomarkers such as chitotriosidase (ChT), GlcSph, and CCL18 have been identified for the diagnosis and monitoring of GD. At the same time, multi-omics-based technologies have improved our understanding of the pathophysiology of GD and helped in the identification of potential biomarkers and therapeutic targets. Emerging technologies like gene therapy, pharmacological chaperones, and nanovesicle-based systems show promise but need to be validated.</p> Conclusion <p>Although considerable progress has been made in GD research, major gaps still exist in terms of biomarker validation, managing neuronopathic disease, and epidemiology. The combination of multi-omics approaches and translational models could facilitate precise diagnosis and therapy.</p> Graphical Abstract <p></p>

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Gaucher Disease: Insights from Preclinical Models to Omics-Based Biomarker Discovery and Future Directions

  • 期刊论文

  • 发表日期：

    2026年4月27日

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  • Vinitha D’Souza,
  • Shobha Dagamajalu,
  • T. S. Keshava Prasad

摘要

Background

Gaucher disease (GD) is a common lysosomal storage disorder caused by mutations in the glucocerebrosidase-1 (GBA1) gene, resulting in the deficiency of the lysosomal enzyme β-glucocerebrosidase (GCase) and the subsequent accumulation of glucosylceramide (GluCer) and glucosylsphingosine (GlcSph; Lyso-Gb1). However, major gaps remain regarding the management of neurological symptoms and the validation of effective biomarkers.

Objective

This review summarizes current insights from preclinical models and omics-based approaches to understand GD pathophysiology, biomarker discovery, and emerging therapeutic strategies.

Methods

A comprehensive literature review was performed focusing on preclinical models (mouse, zebrafish, Drosophila, medaka, canine, and ovine) and omics technologies, including proteomics, genomics, and metabolomics. Relevant studies on biomarkers and therapies were critically analysed.

Results

The preclinical model has shed light on several important pathogenic mechanisms, including lipid accumulation, immune dysfunction, and neuroinflammation. There have been advances in the treatment of GD using enzyme replacement therapy (ERT) and substrate reduction therapy (SRT), but these are limited by their high cost, lack of accessibility, and lack of effectiveness against the neuronopathic variants. Different biomarkers such as chitotriosidase (ChT), GlcSph, and CCL18 have been identified for the diagnosis and monitoring of GD. At the same time, multi-omics-based technologies have improved our understanding of the pathophysiology of GD and helped in the identification of potential biomarkers and therapeutic targets. Emerging technologies like gene therapy, pharmacological chaperones, and nanovesicle-based systems show promise but need to be validated.

Conclusion

Although considerable progress has been made in GD research, major gaps still exist in terms of biomarker validation, managing neuronopathic disease, and epidemiology. The combination of multi-omics approaches and translational models could facilitate precise diagnosis and therapy.

Graphical Abstract