Gaucher Disease
Gaucher disease is a rare inherited metabolic disorder that manifests through the accumulation of glucocerebroside, a fatty substance, within various organs and tissues, notably affecting the liver, spleen, and bone marrow. Our company stands out as a leader in rare diseases, including conditions like Gaucher disease, offering a comprehensive service to researchers and scientists that cater to the unique needs of the rare disease research community.
Overview of Gaucher Disease
Gaucher disease is an autosomal recessive disorder, with a global birth prevalence of approximately 1.5 cases per 100,000 live births, and stems from the deficiency of the enzyme glucocerebrosidase, also known as acid beta-glucosidase. The enzyme's crucial role in breaking down glucocerebroside into glucose and ceramide is compromised, leading to the development of three primary subtypes of Gaucher disease: Type 1 (non-neuropathic or non-cerebral), Type 2 (acute neuropathic), and Type 3 (subacute neuropathic).
Fig.1 Overview of Gaucher disease. (Kong, W., et al., 2022)Pathogenesis of Gaucher Disease
The complex pathogenesis of Gaucher disease originates from mutations in the GBA1 gene, responsible for encoding lysosomal acid β-glucocerebrosidase. Dysfunction in the hydrolysis of sphingolipid glucosylceramide (GlcCer) within lysosomes, especially macrophages, results in the enlargement of these cells, forming characteristic Gaucher cells, laden with lipids. This aberrant accumulation of GlcCer disrupts normal organ functions, precipitating a spectrum of debilitating symptoms associated with the disease.
Fig.2 Two pathologies in Gaucher disease. (Kong, W., et al., 2022)Biomarkers Development of Gaucher Disease
Biomarkers serve as indispensable tools in the intricate diagnosis and monitoring of Gaucher disease, offering measurable indicators of disease presence, severity, and progression. These biomarkers provide invaluable insights that guide researchers in formulating effective therapy strategies for individuals.
- Ferritin
- Chitotriosidase
- CCL18
- lyso-Gb1
- MIP-1β
- ACE
Therapeutics Development of Gaucher Disease
| Therapies | Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Enzyme replacement therapy | Imiglucerase and velaglucerase alfa | Recover glucosylceramidase activity with exogenously applied recombinant protein | Glucocerebrosidase | Approved |
| Substrate reduction therapy | Miglustat and eliglustat | Bind active-sites of biosynthesis enzyme to reduce biosynthesis of GlcCer | Glucosylceramidase | Approved |
| Chaperone therapy | Ambroxol | Recovers glucosylceramidase activity by correcting misfolding enzymes | Glucosylceramidase | Phase I trials |
| Gene therapy | AVR-RD-02 | Ex vivo gene therapy that delivers glucosylceramidase beta gene using lentiviral vector | GBA1 | Phase I/II trials |
| AAV9-CMV-Gba | In vivo gene therapy that delivers glucosylceramidase beta gene using AAV9 vector | GBA | Preclinical research | |
| Genome editing | Using editing platforms such as CRISPR/Cas9 system, ZFNs, and TALENs to correct genetic disorders | GBA | Preclinical research |
Our Services
Our team of highly skilled professionals is equipped with the latest knowledge and technologies, and with an animal model and therapeutic development platform, enabling us to deliver cutting-edge solutions tailored to the study of rare diseases. With our commitment to excellence, innovation, and collaboration, we are dedicated to making a meaningful impact on rare diseases.
Therapeutics Development Platforms
Animal Models of Gaucher Disease
Animal models have significantly contributed to our understanding of Gaucher disease and have been crucial in the development and evaluation of potential therapeutic approaches. Our company provides a variety of animal models of Gaucher disease to provide valuable tools for assessing the safety and efficacy of experimental interventions.
Chemical-induced Models
The chemical induction model of Gaucher disease involves the administration of certain compounds such as conduritol-B-epoxide (CBE) and ME656, which interfere with the activity of the enzyme glucocerebrosidase.
Optional Models: CBE-induced model; ME656-induced model, etc.
Genetically Engineered Models
Genetic engineering models of Gaucher disease involve the manipulation of the animal's genome by genetic engineering techniques such as CRISPR/Cas9 to introduce specific mutations in the GBA gene.
Optional Models: Gba1 KO model; GbaL444P/L444P model, etc.
Why Choose Us
Our company provides a comprehensive suite of services including pharmacokinetic studies and biosafety evaluation services, to facilitate breakthrough discoveries and accelerate the development of potential therapies.
If you are interested in learning more about our services and how we can support your research endeavors, please do not hesitate to reach out to us for further information.
References
- Cabasso, Or et al. "Animal Models for the Study of Gaucher Disease." International journal of molecular sciences 24.22 (2023): 16035.
- Kong, Weijing et al. "Update of treatment for Gaucher disease." European journal of pharmacology 926 (2022): 175023.
- Giuffrida, Gaetano et al. "Glucosylsphingosine (Lyso-Gb1) as a reliable biomarker in Gaucher disease: a narrative review." Orphanet journal of rare diseases 18.1 (2023): 27.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.