Fabry Disease
Fabry disease causes progressive neurological damage through accumulation of globotriaosylceramide (Gb3) in peripheral nerves and cerebrovascular endothelium. With our deep expertise in Fabry disease therapy development, Protheragen is well positioned to provide tailored solutions and comprehensive support to facilitate your journey from Fabry disease therapy research to commercialization.
Overview of Fabry Disease
Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, which encodes the enzyme α-galactosidase A (α-Gal A). This deficiency leads to the systemic accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosylsphingosine (lyso-Gb3). The disease manifests in two primary clinical forms: classic Fabry disease and late-onset/atypical Fabry disease.
Fig.1 Molecular and cellular alterations involved in pathogenesis of Anderson–Fabry disease. (Tuttolomondo A, et al., 2021)
Pathogenesis of Fabry Disease
Fabry disease results from mutations in the GLA gene leading to α-galactosidase A (α-Gal A) enzyme deficiency, and is biochemically characterized by the pathological accumulation of globotriaosylceramide (Gb3) and lyso-Gb3 in lysosomes. It predominantly affects the vascular endothelium, podocytes, cardiomyocytes, and neurons, leading to progressive multi-organ damage due to lysosomal dysfunction, endothelial damage, and inflammation. The characteristic systemic manifestations, including renal failure, cardiomyopathy, and neuropathic pain, result from this glycolipid deposition pathology.
Fig.2 Pathophysiology of Fabry disease. (Lerario S, et al., 2024)
Therapeutic Development for Fabry Disease
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Pegunigalsidase alfa-iwxj | Cross-linked recombinant α-galactosidase A with prolonged circulation half-life | Lysosomal α-Gal A enzyme | Approved |
| Galafold (migalastat) | Pharmacological chaperone that stabilizes amenable mutant α-Gal A variants | Mutant α-Gal A proteins | Approved |
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
Recognizing the complexity of diagnosing and treating Fabry disease, Protheragen is committed to building a team of experts to provide cutting-edge diagnostic and therapeutic development solutions. Our commitment lies in providing a variety of customized therapy development services to meet the diverse research needs of our customers. We also excel in generating precise disease models that are carefully engineered to replicate the unique features of Fabry disease.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- GLA Knockout Mouse Model: Complete deletion of α-Gal A gene, leading to systemic Gb3 accumulation.
- G3Stg/GlaKO Mouse Model: Combines GLA KO with human A4GALT transgene to enhance Gb3 synthesis, closely replicating human disease biochemistry.
At Protheragen, we are dedicated to supporting the development of innovative therapies through comprehensive preclinical research services. Our expertise spans pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies, ensuring a thorough evaluation of your therapeutic candidates. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Tuttolomondo A, Simonetta I, Riolo R, et al. Pathogenesis and molecular mechanisms of Anderson–Fabry disease and possible new molecular addressed therapeutic strategies[J]. International Journal of Molecular Sciences, 2021, 22(18): 10088.
- Lerario S, Monti L, Ambrosetti I, et al. Fabry disease: a rare disorder calling for personalized medicine[J]. International Urology and Nephrology, 2024, 56(10): 3161-3172.