Aspartylglycosaminuria (AGU), the most common lysosomal disorder of
glycoprotein degradation, is caused by deficient activity of
glycosylasparaginase (AGA). AGA-deficient mice share most of the clinical, biochemical and histopathologic characteristics of human AGU disease. In the current study, recombinant human AGA administered i.v. to adult AGU mice disappeared from the systemic circulation of the animals in two phases predominantly into non-neuronal tissues, which were rapidly cleared from storage compound
aspartylglucosamine. Even a single AGA injection reduced the amount of
aspartylglucosamine in the liver and spleen of AGU mice by 90% and 80%, respectively. Quantitative biochemical analyses along with histological and immunohistochemical studies demonstrated that the pathophysiologic characteristics of AGU were effectively corrected in non-neuronal tissues of AGU mice during 2 wk of AGA
therapy. At the same time, AGA activity increased to 10% of that in normal brain tissue and the accumulation of
aspartylglucosamine was reduced by 20% in total brain of the treated animals. Immunohistochemical studies suggested that the corrective
enzyme was widely distributed within the brain tissue. These findings suggest that AGU may be correctable by
enzyme therapy.-Dunder, U., Kaartinen, V., Valtonen, P., Väänänen, E., Kosma, V.-M., Heisterkamp, N., Groffen, J., Mononen, I.
Enzyme replacement therapy in a mouse model of
aspartylglycosaminuria.