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

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

Research output: Contribution to journalReview article

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)406-414
Number of pages9
JournalGene Therapy
Volume10
Issue number5
DOIs
Publication statusPublished - 2003 Mar 1
Externally publishedYes

Keywords

  • Adenovirus
  • Gene therapy
  • Mucopolysaccharidosis
  • Neonatal treatment

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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