Murine mucopolysaccharidosis VII: Impact of therapies on the phenotype, clinical course, and pathology in a model of a lysosomal storage disease

The mucopolysaccharidoses are a group of lysosomal storage diseases caused by deficiency of an enzyme required for the normal degradation of glycosami noglycans. Patients with mucopolysacchariclosis typically have widespread l ysosomal storage, skeletal and central nervous system disease, and hepatosp lenomegaly. Some patients with mucopolysaccharidosis may benefit from enzym e replacement therapy or bone marrow transplantation. Animal models of muco polysacchariclosis have proven valuable for the evaluation of the effective ness of potential treatments for patients with lysosomal storage disease. A murine model of MPS VII (Sly syndrome) has proven particularly useful beca use of its well-defined genetics and its well-characterized clinical, patho logic, and biochemical alterations, which resemble those seen in patients w ith mucopolysaccharidosis. Correction of these alterations forms the basis for evaluation of the effectiveness of novel treatments. A wide range of th erapies have been tested using this model, including enzyme replacement the rapy, bone marrow, stem cell, and neural progenitor cell transplantation, a nd a variety of viral-mediated gene therapies. The inferences drawn from th ese therapeutic studies using the murine MPS VII model are likely generaliz able to other lysosomal storage diseases.