Animal models for mucopolysaccharidoses and their clinical relevance

Area of Science:

• Biochemistry
• Genetics
• Veterinary Medicine

Background:

• Mucopolysaccharidoses (MPS) are a group of genetic disorders characterized by the accumulation of glycosaminoglycans (GAGs) due to deficiencies in specific lysosomal enzymes.
• MPS II, caused by iduronate-2-sulphatase deficiency, was the first identified human MPS, while MPS VI was the first recognized in animals.

Purpose of the Study:

• To review the utility of animal models in understanding MPS pathogenesis and evaluating therapeutic strategies.
• To highlight the similarities between human and animal MPS models, including genetic inheritance patterns and disease pathology.

Main Methods:

• Review of naturally occurring and genetically engineered animal models for various MPS types.
• Comparison of disease characteristics and genetic inheritance (autosomal recessive, X-linked) between human and animal MPS.
• Evaluation of therapeutic approaches tested in animal models, including enzyme replacement therapy, bone marrow transplantation, and gene transfer.

Main Results:

• Most MPS types, except MPS IIIC and IX, have been described in animals or created via knock-out technology.
• Animal models exhibit similar disease pathology to human MPS, making them valuable for research.
• Large animal models offer advantages due to genetic diversity and the ability to assess long-term treatment effects.

Conclusions:

• Animal models are indispensable tools for investigating MPS pathogenesis and for preclinical testing of novel therapies.
• Therapeutic strategies such as enzyme replacement, bone marrow transplantation, and gene therapy have shown promise in animal models.
• Continued development and utilization of animal models will accelerate the discovery of effective treatments for human MPS.