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Animal Models for Fabry's Disease

Our company provides one-stop animal model development services for the evaluation of new therapeutics for Fabry's disease. We are dedicated to building appropriate animal models of Fabry's disease for testing and screening candidate therapies through gene manipulation, RNA manipulation, and substrate administration technologies. Our preclinical research experts will work closely with you to obtain meaningful data from Fabry's animal model studies to provide new insights into associated pathogenic mechanisms and advance the development of potential therapies in clinical studies.

Background

Fabry's disease, also known as Anderson-Fabry syndrome, is a multisystemic lysosomal storage disease induced by mutations in the X-chromosome-linked GLA gene. In Fabry's disease, defects in the lysosomal enzyme α-galactosidase A (encoded by the GLA gene) lead to abnormal accumulation of globotriaosylceramide (Gb3) in various tissues of the body. Accumulation of Gb3 results in many complications, such as neurological (pain), cardiovascular (arrhythmias), renal (kidney failure), cochlear vestibular and cerebrovascular (transient ischemic attacks and strokes) complications.

Current treatment of Fabry's disease consists mainly of symptomatic or preventive treatment of the affected organs as well as enzyme replacement therapy and enzyme-enhanced therapy aimed at removing Gb3 from storage sites. No specific treatment has been developed for patients with Fabry's disease at this time. In this context, the development of animal models is valuable to explore therapeutic strategies for patients with Fabry's disease.

Fig. 1 Fabry rat generation and activities of selected lysosomal enzymes.

Fig. 1 Fabry rat generation and activities of selected lysosomal enzymes. (Miller J J, et al., 2018)

Disease Modeling Services

Our researchers provide technical support for our clients to develop multiple disease models of Fabry's disease, providing useful information to study the underlying mechanisms that may lead to Fabry's disease. We also provide histological analysis, lysosomal enzyme assay, determination of Gb3 content and serum globotriaosylsphingosine (lyso-Gb3), glycolipid analysis, Western blot analysis, and SDS-PAGE to characterize disease models. Our modeling services include, but are not limited to:

  • Modeling Fabry's disease in mice
    We help our clients generate α-Galactosidase A-knockout (GLAko) mice through gene targeting. These mutant mice have similar pathophysiological processes to Fabry's disease patients.
    We help our clients generate symptomatic mice (G3Stg/GLAko) by crossbreeding GLAko mice with human Gb3 synthase (G3S)-transgenic mice (TgG3S mice). These models exhibit progressive renal impairment and are suitable for the study of Fabry's disease.
  • Modeling Fabry's disease in rat
    We help our clients generate dark agouti rat models with the knockout of α-Galactosidase A using CRISPR/Cas9 technology to study Fabry's disease. In addition to elevated Gb3 and lyso-Gb3, our generated models also exhibit clinical manifestations such as ocular defects, renal dysfunction, cardiac dysfunction, and mechanical hypersensitivity.

Preclinical Research Services

We help our clients generate suitable animal models to study the therapeutic effects of multiple treatments for Fabry's disease:

  • Enzyme replacement therapy
  • Bone marrow transplantation
  • Gene therapy
  • Substrate reduction therapy (SRT)
  • Pharmacological chaperone therapy

We provide the following testing and analysis of disease models:

  • Measurement of the activity of α-Galactosidase A in different organs, including the brain, spinal cord, heart, liver, and kidney
  • Analysis of Gb3 levels in different tissues
  • Analysis of abnormal pain sensation in Fabry animals
  • Analysis of motor, affective, and cognitive impairments in Fabry animals

As a biotechnology company in the field of rare diseases, our researchers have made many efforts to develop and characterize animal models of Fabry's disease. Our custom animal models can be tailored to specific research questions and our preclinical studies can help to accelerate the development of new therapies for Fabry's disease. If you are interested in our services, please contact us for more details.

Reference

  • Miller, J.J.; et al. Neuropathic pain in a Fabry disease rat model. JCI insight, 2018, 3(6).

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

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