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Updated: May 8, 2026
Delivery of Therapeutic Agents Through Intracerebroventricular (ICV) and Intravenous (IV) Injection in Mice
Published on: October 3, 2011
Enzyme replacement therapy for murine mucopolysaccharidosis type VII leads to improvements in behavior and auditory
L H O'Connor1, L C Erway, C A Vogler
1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Abstract:
Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is one of a group of lysosomal storage diseases that share many clinical features, including mental retardation and hearing loss. Lysosomal storage in neurons of the brain and the associated behavioral abnormalities characteristic of a murine model of MPS VII have not been shown to be corrected by either bone marrow transplantation or gene therapy. However, intravenous injections of recombinant beta-glucuronidase initiated at birth reduce the pathological evidence of disease in MPS VII mice. In this study we present evidence that enzyme replacement initiated at birth improved the behavioral performance and reduced hearing loss in MPS VII mice. Enzyme-treated MPS VII mice performed similarly to normal mice and significantly better than mock- treated MPS VII mice in every phase of the Morris Water Maze test. In addition, the auditory function of treated MPS VII mice was dramatically improved, and was indistinguishable from normal mice. These data indicate that some of the learning, memory, and hearing deficits can be prevented in MPS VII mice if enzyme replacement therapy is initiated early in life. These data also provide functional correlates to the biochemical and histopathological improvements observed after enzyme replacement therapy.
Insights
Early enzyme replacement therapy for Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) in mice improved cognitive function and hearing. This treatment prevented learning, memory, and auditory deficits, offering a promising therapeutic approach.
Area of Science:
- Biochemistry
- Genetics
- Neuroscience
Background:
- Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is a lysosomal storage disease characterized by neurological and auditory deficits.
- Previous treatments like bone marrow transplantation and gene therapy have not corrected neuronal storage or behavioral abnormalities in MPS VII mouse models.
- Intravenous recombinant beta-glucuronidase at birth showed promise in reducing pathological evidence of MPS VII in mice.
Purpose of the Study:
- To investigate the efficacy of early-initiated enzyme replacement therapy (ERT) using recombinant beta-glucuronidase in a murine model of MPS VII.
- To assess the impact of ERT on behavioral performance and auditory function in MPS VII mice.
Main Methods:
- MPS VII mice received intravenous injections of recombinant beta-glucuronidase starting at birth.
- Behavioral testing was conducted using the Morris Water Maze to evaluate learning and memory.
- Auditory function was assessed to determine the extent of hearing loss improvement.
Main Results:
- Enzyme-treated MPS VII mice exhibited performance in the Morris Water Maze comparable to normal mice and significantly better than mock-treated MPS VII mice.
- Auditory function in treated MPS VII mice was dramatically improved, becoming indistinguishable from that of normal mice.
- ERT initiated at birth prevented learning, memory, and hearing deficits in the MPS VII mouse model.
Conclusions:
- Early initiation of enzyme replacement therapy with recombinant beta-glucuronidase can prevent or ameliorate learning, memory, and hearing deficits in MPS VII mice.
- These findings provide functional evidence supporting the biochemical and histopathological improvements observed with ERT in MPS VII.
- This study highlights the potential of early ERT as a therapeutic strategy for Sly syndrome.
