Improvement of skeletal lesions in mice with mucopolysaccharidosis type VII by neonatal adenoviral gene transfer

Neonatal gene transfer using adenovirus vectors expressing human β-glucuronidase (AxCAhGUS) resulted in pathological improvement in multiple visceral organs of mice with mucopolysaccharidosis type VII (MPSVII). However, the therapeutic effect on skeletal deformities and growth retardation, the major clinical symptoms in MPSVII, was not fully investigated by biochemical and histopathological analyses. In this study, we injected AxCAhGUS into a murine model of MPSVII (B6/MPSVII) within 24 h of birth and evaluated the therapeutic effects on skeletal deformities and growth retardation. High levels of β-glucuronidase (GUSB) activity (approximately threefold higher than normal GUSB activity) were observed in the articular cartilage of the mice 30 days after the treatment. Histopathological study in the knee joints showed elimination of vacuole cells in the articular cartilage and growth plate. Subchondral bone near the articular surface was almost normal in the treated MPSVII mice. Long-term observation (for 140 days after treatment) indicated that characteristic phenotypes such as flattened face, hunched stature, and shortening of bone length in the treated mice were almost normal. These results demonstrate that a single injection of adenovirus vector into neonatal MPSVII mice is sufficient for long-term normalization of skeletal deformities and effective in pathological correction of the articular cartilage and growth plate.