Fabry Disease

Fabry Disease (FD) is an X-linked lysosomal storage disorder caused by GLA gene mutations, leading to α-galactosidase A deficiency and progressive globotriaosylceramide (Gb3) accumulation in kidneys, heart, and nerves. Protheragen is dedicated to advancing therapeutic solutions for rare kidney diseases. Here, we present our comprehensive service offerings for Fabry disease.

Overview of Fabry Disease

Fabry Disease is a rare X-linked, hereditary, lysosomal storage disorder with an estimated prevalence of 1 in 1, 000 to 1 in 9,000. Fabry Disease is associated with a deficiency of the α-galactosidase A enzyme as well as the accumulation of a lipids such as globotriaosylceramide (Gb3) in numerous cell types in the body. It is associated with a wide variety of signs and symptoms. Importantly, the disease can progress to life threatening illnesses such as chronic kidney disease, ischemic heart disease, and cerebrovascular disease.

Pathogenesis of Fabry Disease

The pathogenic variants in the GLA gene, responsible for producing α-galactosidase A (α-Gal A) enzyme, results in the disease. The gene is located on the X chromosome. A functional deficiency or complete absence of α-Gal A results in the progressive deposition of globotriaosylceramide (Gb3) and globotriaosylsphingosine (LysoGb3) within cellular lysosomes.

Fig.1 Pathophysiology of Fabry disease. (Lerario et al., 2024)

Within the kidneys, the accumulation of Gb3 and LysoGb3 occurs in almost all renal epithelial cell types, such as podocytes, glomerular endothelial cells, mesangial cells, and tubular cells. This accumulation initiates a series of cellular dysfunction, inflammation, oxidative stress, and, in the end, fibrosis in the tissue. Podocytes, which are terminally differentiated, long-lived, and therefore age-accumulate cells, are particularly vulnerable to excessive Gb3 accumulation which leads to cell death. This loss contributes greatly to the development of proteinuria and the decline in kidney function. Tubular cells which are also greatly impacted due to their energetic nature, also contribute to the atrophy of the tubules and interstitial fibrosis. This cellular damage and the body's inflammatory reaction to it eventually leads to progressive glomerulosclerosis and the development of cysts in the kidneys, increasing the risk of chronic kidney disease and in the long run, end-stage renal disease.

Therapeutics Development for Fabry Disease

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

Protheragen specializes in developing advanced disease models for Fabry disease and offers comprehensive preclinical therapeutic development services. We focus on elucidating the diverse genetic and metabolic impacts of GLA mutations that lead to the multi-systemic manifestations of Fabry disease.

Therapeutic Development Platforms for Fabry Disease

• Small Molecule Drug
• Cell Therapy
• Gene Therapy

• Therapeutic Antibody
• Therapeutic Peptide
• Therapeutic Protein

Disease Models Development for Fabry Disease

Protheragen offers innovative and comprehensive disease models to advance the preclinical research of Fabry disease. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the α-Gal A deficiency and Gb3 accumulation that cause Fabry disease, supporting extensive drug discovery and mechanism-based investigations focused on lysosomal function and organ pathology.

Cell-based & Organoid Models

• GLA^−/− human podocytes
• GLA-mutant renal endothelial cells
• GLA^R227X tubular epithelial cells
• Vascularized Fabry tubuloids

Animal Models

• Gla^KO mice
• Human GLA^p.N215S transgenic rats
• Podocyte-specific Gla^−/− mice
• Zebrafish gla^−/− mutants

Drug Safety Evaluation & Pharmacokinetics Services

In Vitro ADME Services

• Metabolic Stability Assay
• Plasma Protein Binding
• Renal Tubular Epithelial Cell Uptake & Efflux
• Drug-Transporter Interaction Profiling
• Cellular Permeability

In Vivo Pharmacokinetics Services

• Systemic Pharmacokinetics
• Kidney Tissue Distribution and Retention
• Renal Clearance and Excretion Studies
• Urinary Metabolite Profiling
• Blood-to-Plasma Ratio

Drug Safety Evaluation

• General Toxicology Evaluation
• Genetic Toxicology Evaluation
• Developmental and Reproductive Toxicity Evaluation

• Immunogenicity and Immunotoxicity Evaluation
• Local Toxicity Evaluation
• Phototoxicity Evaluation

• Tissue Cross-Reactivity Evaluation
• Safety Pharmacology Evaluation
• Toxicokinetic Evaluation

Protheragen provides integrated preclinical development solutions specifically designed for research in rare genetic and metabolic disorders like Fabry disease. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation.

Contact us today to accelerate your Fabry disease research with end-to-end solutions.

References

1. Lerario, S., et al. "Fabry Disease: A Rare Disorder Calling for Personalized Medicine." Int Urol Nephrol 56.10 (2024): 3161-72.
2. van der Veen, S. J., et al. "Developments in the Treatment of Fabry Disease." J Inherit Metab Dis 43.5 (2020): 908-21.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.