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We demonstrated that biochemical alterations in the brains of MPS II mice are not corrected by bone marrow transplantation (BMT) or enzyme replacement therapy, although BMT has been shown to be effective for other neurodegenerative MPSs, such as Hurler syndrome. In this study, we demonstrated that lentiviral isogeneic hematopoietic stem cell (HSC) gene therapy corrected neuronal manifestations by ameliorating lysosomal storage and autophagic dysfunction in the brains of MPS II mice. IDS-transduced HSCs increased enzyme activity both in various visceral organs and the CNS. Decreased levels of GAGs were observed in many organs, including cerebra, after transplantation of IDS-transduced HSCs. In addition, lentiviral HSC gene therapy normalized the secondary accumulation of autophagic substrates, such as p62 and ubiquitin\u2013protein conjugates, in cerebra. Furthermore, in contrast to naive MPS II mice, there was no deterioration of neuronal function observed in transplant recipients. These results indicated that lentiviral HSC gene therapy is a promising approach for the treatment of CNS lesions in MPS II.<\/jats:p>","DOI":"10.1089\/hum.2014.158","type":"journal-article","created":{"date-parts":[[2015,3,12]],"date-time":"2015-03-12T02:23:10Z","timestamp":1426126990000},"page":"357-366","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":50,"title":["Hematopoietic Stem Cell Gene Therapy Corrects Neuropathic Phenotype in Murine Model of Mucopolysaccharidosis Type II"],"prefix":"10.1177","volume":"26","author":[{"given":"Taichi","family":"Wakabayashi","sequence":"first","affiliation":[{"name":"Jikei University School of Medicine","place":["Japan"]},{"name":"Jikei University School of Medicine","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohta","family":"Shimada","sequence":"additional","affiliation":[{"name":"Jikei University School of Medicine","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumasa","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Kitasato University School of Medicine","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Jikei University School of Medicine","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Jikei University School of Medicine","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Jikei University School of Medicine","place":["Japan"]},{"name":"Jikei University School of Medicine","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshikatsu","family":"Eto","sequence":"additional","affiliation":[{"name":"Institute of Neurological Disorders","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Ida","sequence":"additional","affiliation":[{"name":"Jikei University School of Medicine","place":["Japan"]},{"name":"Jikei University School of Medicine","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toya","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Jikei University School of Medicine","place":["Japan"]},{"name":"Jikei University School of Medicine","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,3,11]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000232477.37660.fb"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.08.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181fea459"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9317-5"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2003.09.003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1189"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00710053"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005525931994"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.11.041"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.09.013"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1171242"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233158"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233151"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/987980"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-278234"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.82"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0641-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.10.006"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300180"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.136"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.05.005"},{"key":"e_1_3_3_23_2","unstructured":"Shimada Y Wakabayashi T Akiyama K et al. 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