TY - JOUR
T1 - 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
AU - Kamata, Y.
AU - Tanabe, A.
AU - Kanaji, A.
AU - Kosuga, M.
AU - Fukuhara, Y.
AU - Li, X. K.
AU - Suzuki, S.
AU - Yamada, M.
AU - Azuma, N.
AU - Okuyama, T.
N1 - Funding Information:
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.
PY - 2003/3
Y1 - 2003/3
N2 - 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.
AB - 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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U2 - 10.1038/sj.gt.3301869
DO - 10.1038/sj.gt.3301869
M3 - Review article
C2 - 12601395
AN - SCOPUS:0037344452
SN - 0969-7128
VL - 10
SP - 406
EP - 414
JO - Gene therapy
JF - Gene therapy
IS - 5
ER -