{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T23:02:13Z","timestamp":1770505333937,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,9,15]],"date-time":"2012-09-15T00:00:00Z","timestamp":1347667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease due to \u03b1\u2010L\u2010iduronidase (IDUA) deficiency that results in the accumulation of glycosaminoglycans (GAG). Systemic gene therapy to MPS I mice can reduce lysosomal storage in the brain, but few data are available regarding the effect upon behavioral function. We investigated the effect of gene therapy with a long\u2010terminal\u2010repeat (LTR)\u2010intact retroviral vector or a self\u2010inactivating (SIN) vector on behavioral function in MPS I mice. The LTR vector was injected intravenously to 6\u2010week\u2010old MPS I mice, and the SIN vector was given to neonatal or 6\u2010week\u2010old mice. Adult\u2010LTR, neonatal\u2010SIN, and adult\u2010SIN\u2010treated mice achieved serum IDUA activity of 235\u2009\u00b1\u200920 (84\u2010fold normal), 127\u2009\u00b1\u200910, and 71\u2009\u00b1\u20097 U\/ml, respectively. All groups had reduction in histochemical evidence of lysosomal storage in the brain, with the adult\u2010LTR group showing the best response, while adult\u2010LTR mice had reductions in lysosomal storage in the cristae of the vestibular system. Behavioral evaluation was performed at 8 months. Untreated MPS I mice had a markedly reduced ability to hold onto an inverted screen or climb down a pole. LTR\u2010vector\u2010treated mice had marked improvements on both of these tests, whereas neonatal\u2010SIN mice showed improvement in the pole test. We conclude that both vectors can reduce brain disease in MPS I mice, with the LTR vector achieving higher serum IDUA levels and better correction. Vestibular abnormalities may contribute to mobility problems in patients with MPS I, and gene therapy may reduce symptoms.<\/jats:p>","DOI":"10.1007\/s10545-012-9530-x","type":"journal-article","created":{"date-parts":[[2012,9,15]],"date-time":"2012-09-15T02:59:23Z","timestamp":1347677963000},"page":"499-512","source":"Crossref","is-referenced-by-count":19,"title":["Retroviral\u2010vector\u2010mediated gene therapy to mucopolysaccharidosis I mice improves sensorimotor impairments and other behavioral deficits"],"prefix":"10.1002","volume":"36","author":[{"given":"Guilherme","family":"Baldo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Washington University School of Medicine 660 South Euclid Avenue St. Louis MO 63110 USA"},{"name":"Gene Therapy Center Hospital de Clinicas de Porto Alegre Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David 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