2015年3月
Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I
BLOOD
- 巻
- 125
- 号
- 10
- 開始ページ
- 1662
- 終了ページ
- 1671
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1182/blood-2014-06-581207
- 出版者・発行元
- AMER SOC HEMATOLOGY
Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept inmucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of alpha-L-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPSIH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring alpha-L-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear.
- リンク情報
- ID情報
-
- DOI : 10.1182/blood-2014-06-581207
- ISSN : 0006-4971
- eISSN : 1528-0020
- PubMed ID : 25298037
- Web of Science ID : WOS:000354619800024