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大学・研究所にある論文を検索できる 「Ex-vivo gene therapy treats bone complications of mucopolysaccharidosis type II mouse models through bone remodeling reactivation」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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Ex-vivo gene therapy treats bone complications of mucopolysaccharidosis type II mouse models through bone remodeling reactivation

和田, 美穂 東京慈恵会医科大学 DOI:info:doi/10.1016/j.omtm.2020.09.012

2021.10.22

概要

Mucopolysaccharidosis type II is a disease caused by organ accumulation of glycosaminoglycans due to iduronate 2-sulfa- tase deficiency. This study investigated the pathophysiology of the bone complications associated with mucopolysaccharidosis II and the effect of lentivirus-mediated gene therapy of hemato- poietic stem cells on bone lesions of mucopolysaccharidosis type II mouse models in comparison with enzyme replacement therapy. Bone volume, density, strength, and trabecular num- ber were significantly higher in the untreated mucopolysac- charidosis type II mice than in wild-type mice. Accumulation of glycosaminoglycans caused reduced bone metabolism. Spe- cifically, persistent high serum iduronate 2-sulfatase levels and release of glycosaminoglycans from osteoblasts and osteoclasts in mucopolysaccharidosis type II mice that had un- dergone gene therapy reactivated bone lineage remodeling, subsequently reducing bone mineral density, strength, and trabecular number to a similar degree as that observed in wild-type mice. Bone formation, resorption parameters, and mineral density in the diaphysis edge did not appear to have been affected by the irradiation administered as a pre-treat- ment for gene therapy. Hence, the therapeutic effect of gene therapy on the bone complications of mucopolysaccharidosis type II mice possibly outweighed that of enzyme replacement therapy in many aspects.

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