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Long-term normalization in the central nervous system, ocular manifestations, and skeletal deformities by a single systemic adenovirus injection into neonatal mice with mucopolysaccharidosis VII

Gene Therapy volume 10, pages 406–414 (2003)Cite this article

Abstract

Systemic injection of an adenovirus vector into adult mice resulted in pathological improvements in multiple visceral organs of mice with mucopolysaccharidosis VII; however, no therapeutic efficacy was observed for mental retardation, skeletal deformities, corneal clouding, and retinal degeneration. In this study, an adenovirus vector expressing human β-glucuronidase was injected into mice with mucopolysaccharidosis VII within 24 h of birth, and therapeutic efficacy was evaluated. In the brains of the mice, more than 20% of GUSB activity was maintained for at least 20 weeks after birth, and histopathological analysis showed no obvious lysosomal storage. Furthermore, no vacuolated cells were detected in corneal stroma and retinal pigment epithelium in the eyes of the mice treated in the neonatal period, while pathological improvement was not observed in adult MPSVII mice that received similar treatments. The treated mice also lacked characteristic facial skeletal deformities, and radiographic analysis demonstrated that their facial and cranial bones were morphologically normal. These results indicate that a single systemic adenovirus injection in the neonatal period could prevent the progression of mental retardation, corneal clouding, retinal degeneration, and skeletal deformities, all of which are frequently observed clinical manifestations and difficult to treat in adulthood.

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Acknowledgements

We thank Drs Y Kanegae and I Saito for recombinant adenovirus constructs and Dr J Miyazaki for the CAG promoters. This work was supported in part by grants for Pediatric Research from the Ministry of Health, Labor, and Welfare, Japan, and by grants for Research on Health Sciences focusing on Drug Innovation from the Japan Health Sciences Foundation.

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Authors and Affiliations

  1. National Research Institute for Child Health and Development, Tokyo, Japan

    Y Kamata, A Tanabe, A Kanaji, M Kosuga, Y Fukuhara, X-K Li, S Suzuki, M Yamada, N Azuma & T Okuyama

  2. National Center for Child Health and Development, Japan

    Y Kamata, M Kosuga, N Azuma & T Okuyama

  3. Department of Pediatrics, Keio University School of Medicine, Japan

    M Kosuga, Y Fukuhara & T Okuyama

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  1. Y Kamata
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Kamata, Y., Tanabe, A., Kanaji, A. et al. Long-term normalization in the central nervous system, ocular manifestations, and skeletal deformities by a single systemic adenovirus injection into neonatal mice with mucopolysaccharidosis VII. Gene Ther 10, 406–414 (2003). https://doi.org/10.1038/sj.gt.3301869

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