Gaucher Disease
Gaucher disease (types 2 and 3) causes neuroinflammation, neuronal apoptosis and α-synuclein aggregation, which results in neurological deficits. Drawing on our pioneering work in Gaucher disease, Protheragen is currently developing modern therapies aimed at improving the treatment outcomes of Gaucher disease. We work alongside you as a partner in Gaucher disease medication development research and offer you unparalleled support that fulfills your research requirements.
Introduction to Gaucher Disease
Gaucher disease is an autosomal recessive lysosomal storage disorder, which derives from mutations in the GBA1 gene found on chromosome 1q22. This results in the underactive enzyme of GCase, or glucocerebrosidase. This underactivity results in the pathological accumulation of glucocerebroside (Gb1) as well as its deacylated derivative, glucosylsphingosine (Lyso-Gb1), which builds up in macrophages, producing distinct "Gaucher cells." Gaucher disease is three clinically distinct subtypes:
| Subtypes | Prevalence | Onset | CNS Involvement | Key Mutations |
| Type 1 (Non-neuronopathic GD) | ~90% of cases | Childhood/adulthood | None | p.N370S |
| Type 2 (Acute Neuronopathic GD) | <1% | Infancy (0-6 months) | Severe (brainstem dysfunction, seizures) | p.L444P, c.84dupG |
| Type 3 (Chronic Neuronopathic GD) | ~5-10% | Childhood/adolescence | Progressive (oculomotor apraxia, myoclonus, dementia) | p.L444P, p.D409H |
Pathogenesis of Gaucher Disease
Gaucher disease occurs from biallelic mutations in GBA1 gene which results in deficient glucocerebrosidase (GCase) activity. This results in the accumulation of glucosylceramide (Gb1) and neurotoxic glucosylsphingosine (Lyso-Gb1) within macrophages. These cells then transform into lipid-laden "Gaucher cells" which infiltrate the liver, spleen, and bone marrow. Of the neuronopathic forms, Types 2 and 3 exhibit further central nervous system (CNS) pathology due to neuroinflammation, calcium dysregulation, and α-synuclein aggregation from Lyso-Gb1 mediators.
Fig.2 Schematic representation of the Gaucher disease pathophysiology. (Roh J, et al., 2022)
Therapeutic Development for Gaucher Disease
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| CAN103 | Recombinant human glucocerebrosidase engineered for enhanced CNS penetration | Lysosomal glucocerebrosidase (GCase) | NCT05447494 | Phase I/II |
| Venglustat + Cerezyme | Combination therapy: Venglustat (brain-penetrant SRT) inhibits glucosylceramide synthase, while Cerezyme (imiglucerase) provides exogenous GCase | Glucosylceramide synthase + lysosomal GCase | NCT02843035 | Phase III |
| LY-M001 | Gene therapy using AAV9 vector to deliver functional GBA1 gene to CNS and peripheral tissues | GBA1 gene restoration | NCT06162338 | Phase I/II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
At Protheragen, we focus on preclinical research in Gaucher disease, providing comprehensive solutions from biomarker identification to development of targeted therapeutics. Our expertise covers disease modeling, including patient-derived iPSCs, genetically engineered models, and advanced blood-brain barrier (BBB) models for evaluating drug penetration and neuroprotective efficacy. We provide partners with target validation, lead compound optimization, and comprehensive preclinical research services.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Conduritol-B-epoxide (CBE) Induced Model
- Gba1 Knockout Model
- Gba1 Conditional Knockout Model
- Gba1 L444P Knock-in Model
- D409V Point Mutation Model
- Other Models
At Protheragen, we are committed to validating and optimizing therapies for Gaucher disease through preclinical studies including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology to ensure their successful regulatory approval. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Roh J, Subramanian S, Weinreb N J, et al. Gaucher disease–more than just a rare lipid storage disease[J]. Journal of Molecular Medicine, 2022, 100(4): 499-518.