Pompe Disease (PD)

Animal models are a valuable tool for studying Pompe's disease pathophysiology and testing potential therapies. Our company is committed to providing our clients with appropriate animal models for studying this disease. Our custom animal models are designed to mimic the genetic mutations that cause human Pompe's disease, allowing researchers to study the progression of the disease and test potential therapies. These models can be customized to include specific mutations or genetic backgrounds, providing greater flexibility for preclinical studies.

Background

Pompe's disease (also known as glycogen storage disease type II) is caused by mutations in the enzyme encoding the lysosomal enzyme alpha-glucosidase (GAA), resulting in glycogen accumulation in muscles and other organs. The manifestations of Pompe's disease range from mild forms that appear in adulthood to severe forms that appear in infancy and can be fatal. The severity of the disease is related to the amount of residual enzyme activity.

Despite the low incidence, Pompe's disease requires extensive research into pathophysiology. Therefore, the availability of animal models simulating the disease is essential. To date, a variety of naturally occurring animal models of Pompe's disease has been identified, including Brahman cattle and Shorthorn cattle, Lapland dogs, cats, and sheep. In addition, researchers have developed a variety of laboratory animal models that are more suitable for studying Pompe's disease, such as mouse models and rat models. The development of these models has facilitated the design and evaluation of new therapeutic strategies.

Fig. 1 Exacerbation of Pompe disease phenotype in Atg5 DKO is associated with the generation of a potentially toxic product from the transcript lacking exon 3 of the Atg5 gene. (Lim J A, et al., 2017)

Our Services

Our expert team offers a range of services for animal modeling for Pompe's disease, including the development of custom animal models with specific genetic mutations. We also offer characterization services for existing Pompe disease animal models. These services include the evaluation of muscle strength, respiratory function, and other parameters to assess the severity of the disease and the efficacy of potential therapies.

The mouse model has been the most widely used animal model to study the pathophysiology of Pompe's disease and to test potential therapeutic approaches, including enzyme replacement therapy and gene therapy. We have helped our clients develop a variety of mouse models by targeted disruption of the GAA gene as follows:

We help our clients generate genetically engineered mice that do not produce GAA, known as GAA knockout (KO) mice.
We bred GAA KO mice with DBA2/J animals to generate new mouse models (GAA KO^DBA2/J mice) that exhibit many of the key symptoms common to pathogenesis, including muscle weakness, severe respiratory distress, enlarged heart, and premature death.
We generated knockout mouse models in which exon 6 of the GAA gene was replaced by a cassette containing the neomycin resistance gene into exon 6, flanked by the LoxP locus (6^neo/6^neo). These mice have characteristics of the adult and infantile phenotypes of Pompe's disease.
We created mutant mouse models by mating 6^neo/6^neo mice to Cre-producing mice. This model shows abnormalities in lysosomal glycogen storage in the heart and skeletal muscle.
We created mouse models comparable to the 6neo/6neo models in terms of course by targeting exon 14 of the GAA gene (D14neo/D14neo).

Preclinical Research

Enzyme replacement therapy (ERT) has been the primary therapy for this disease for several years. ERT involves the administration of a recombinant form of the GAA enzyme, which is deficient in Pompe's disease. Our animal model can be used to study ERT efficacy and safety, thus approving its use in human Pompe disease.
Gene therapy has emerged as a potential therapy for Pompe's disease. The therapy involves the delivery of a functional copy of the GAA gene to affected muscles using a viral vector. Our animal model can be used to study gene therapy safety and efficacy, leading to promising results in preclinical studies.
Our animal models can also be used to study potential adjunctive therapies for Pompe's disease, including exercise therapy and nutritional interventions. These therapies have shown promise in preclinical studies, leading to further research.

Our company offers a range of services for animal modeling for Pompe's disease, including the development of custom mouse models and the characterization of existing models. Preclinical studies using these models are expected to develop effective methods for treating Pompe's disease. If you are interested in our disease modeling services, please contact us for more information.

Reference

Lim, J. A.; et al. Atg5flox-derived autophagy-deficient model of Pompe disease: does it tell the whole story? Molecular Therapy-Methods & Clinical Development, 2017, 7: 11-14.

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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