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Here, we present a gene therapy strategy using lumbar puncture of AAVrh10 encoding human \u03b2-glucuronidase (AAVrh10-GUSB) to adult MPS VII mice. This minimally invasive technique efficiently delivers the recombinant vector to the cerebrospinal fluid (CSF) with a single intrathecal injection. We show that AAVrh10 delivery to the CSF allows global, stable transduction of CNS structures. In addition, drainage of AAVrh10-GUSB from the CSF to the bloodstream resulted in the transduction of somatic organs such as liver, which provided a systemic \u03b2-glucuronidase source sufficient to achieve serum enzyme activity comparable to wild type mice. \u00df-glucuronidase levels were enough to correct biochemical and histopathological hallmarks of the disease in the CNS and somatic organs at short and long term. Moreover, the progression of the bone pathology was also reduced. Importantly, the biochemical correction led to a significant improvement in the physical, cognitive and emotional characteristics of MPS VII mice, and doubling their life span. Our strategy may have implications for gene therapy in patients with lysosomal storage diseases.<\/jats:p>","DOI":"10.1093\/hmg\/ddz220","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T11:44:24Z","timestamp":1567683864000},"page":"3610-3624","source":"Crossref","is-referenced-by-count":10,"title":["Intrathecal AAVrh10 corrects biochemical and histological hallmarks of mucopolysaccharidosis VII mice and improves behavior and survival"],"prefix":"10.1093","volume":"28","author":[{"given":"G","family":"Pag\u00e8s","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Gim\u00e9nez-Llort","sequence":"additional","affiliation":[{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Garc\u00eda-Lareu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Ariza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Navarro","sequence":"additional","affiliation":[{"name":"Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Department of Animal Health and Anatomy, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Casas","sequence":"additional","affiliation":[{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Chill\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Barcelona, Spain"},{"name":"Vall d\u2019Hebron Research Institute (VHIR), Barcelona\u00a008035,\u00a0Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7205-2796","authenticated-orcid":false,"given":"A","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, Barcelona 08193, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Vall d\u2019Hebron Research Institute (VHIR), Barcelona\u00a008035,\u00a0Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,9,12]]},"reference":[{"key":"2019122311003608600_ref1","first-page":"132","article-title":"Mucopolysaccharidosis VII: postmortem biochemical and pathological findings in a young adult with beta-glucuronidase deficiency","volume":"7","author":"Vogler","year":"1994","journal-title":"Mod. 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