{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:52:29Z","timestamp":1790805149437,"version":"4.1.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pompe disease (PD) is a metabolic myopathy due to acid alpha-glucosidase deficiency and characterized by extensive glycogen storage and impaired autophagy. We previously showed that modulation of autophagy and lysosomal exocytosis by overexpression of the transcription factor EB (<jats:italic>TFEB<\/jats:italic>) gene was effective in improving muscle pathology in PD mice injected intramuscularly with an AAV-TFEB vector. Here we have evaluated the effects of TFEB systemic delivery on muscle pathology and on functional performance, a primary measure of efficacy in a disorder like PD. We treated 1-month-old PD mice with an AAV2.9-MCK-TFEB vector. An animal cohort was analyzed at 3 months for muscle and heart pathology. A second cohort was followed at different timepoints for functional analysis. In muscles from TFEB-treated mice we observed reduced PAS staining and improved ultrastructure, with reduced number and increased translucency of lysosomes, while total glycogen content remained unchanged. We also observed statistically significant improvements in rotarod performance in treated animals compared to AAV2.9-MCK-eGFP-treated mice at 5 and 8 months. Cardiac echography showed significant reduction in left-ventricular diameters. These results show that <jats:italic>TFEB<\/jats:italic> overexpression and modulation of autophagy result in improvements of muscle pathology and of functional performance in the PD murine model, with delayed disease progression.<\/jats:p>","DOI":"10.1038\/s41598-017-15352-2","type":"journal-article","created":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T23:39:03Z","timestamp":1509665943000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["AAV-mediated transcription factor EB (TFEB) gene delivery ameliorates muscle pathology and function in the murine model of Pompe Disease"],"prefix":"10.1038","volume":"7","author":[{"given":"Francesca","family":"Gatto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Tarallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Polishchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Polishchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Carrella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Nusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena Grazia","family":"Alvino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Iacobellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"De Leonibus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Auricchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciana","family":"Diez-Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ballabio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Parenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,8]]},"reference":[{"key":"15352_CR1","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/S0140-6736(08)61555-X","volume":"372","author":"AT van der Ploeg","year":"2008","unstructured":"van der Ploeg, A. T. & Reuser, A. J. Pompe\u2019s disease. Lancet \n                           372, 1342\u20131353, https:\/\/doi.org\/10.1016\/S0140-6736(08)61555-X (2008).","journal-title":"Lancet"},{"issue":"Suppl 1","key":"15352_CR2","first-page":"S42","volume":"47","author":"L Shea","year":"2009","unstructured":"Shea, L. & Raben, N. Autophagy in skeletal muscle: implications for Pompe disease. Int J Clin Pharmacol Ther \n                           47(Suppl 1), S42\u201347 (2009).","journal-title":"Int J Clin Pharmacol Ther"},{"key":"15352_CR3","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1038\/cdd.2012.52","volume":"19","author":"AC Nascimbeni","year":"2012","unstructured":"Nascimbeni, A. C., Fanin, M., Masiero, E., Angelini, C. & Sandri, M. The role of autophagy in the pathogenesis of glycogen storage disease type II (GSDII). Cell Death Differ \n                           19, 1698\u20131708, https:\/\/doi.org\/10.1038\/cdd.2012.52 (2012).","journal-title":"Cell Death Differ"},{"key":"15352_CR4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/ajmg.c.31317","volume":"160C","author":"N Raben","year":"2012","unstructured":"Raben, N., Wong, A., Ralston, E. & Myerowitz, R. Autophagy and mitochondria in Pompe disease: nothing is so new as what has long been forgotten. Am J Med Genet C Semin Med Genet \n                           160C, 13\u201321, https:\/\/doi.org\/10.1002\/ajmg.c.31317 (2012).","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"15352_CR5","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1212\/01.wnl.0000251268.41188.04","volume":"68","author":"PS Kishnani","year":"2007","unstructured":"Kishnani, P. S. et al. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology \n                           68, 99\u2013109, https:\/\/doi.org\/10.1212\/01.wnl.0000251268.41188.04 (2007).","journal-title":"Neurology"},{"key":"15352_CR6","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/S0140-6736(00)02533-2","volume":"356","author":"H Van den Hout","year":"2000","unstructured":"Van den Hout, H. et al. Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet \n                           356, 397\u2013398 (2000).","journal-title":"Lancet"},{"key":"15352_CR7","doi-asserted-by":"publisher","first-page":"e448","DOI":"10.1542\/peds.113.5.e448","volume":"113","author":"JM Van den Hout","year":"2004","unstructured":"Van den Hout, J. M. et al. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics \n                           113, e448\u2013457 (2004).","journal-title":"Pediatrics"},{"key":"15352_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s00415-009-5275-3","volume":"257","author":"S Strothotte","year":"2010","unstructured":"Strothotte, S. et al. Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial. J Neurol \n                           257, 91\u201397, https:\/\/doi.org\/10.1007\/s00415-009-5275-3 (2010).","journal-title":"J Neurol"},{"key":"15352_CR9","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1056\/NEJMoa0909859","volume":"362","author":"AT van der Ploeg","year":"2010","unstructured":"van der Ploeg, A. T. et al. A randomized study of alglucosidase alfa in late-onset Pompe\u2019s disease. 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J Biol Chem \n                           288, 1428\u20131438, https:\/\/doi.org\/10.1074\/jbc.M112.438663 (2013).","journal-title":"J Biol Chem"},{"key":"15352_CR14","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1038\/mt.2009.37","volume":"17","author":"Y Zhu","year":"2009","unstructured":"Zhu, Y. et al. Glycoengineered acid alpha-glucosidase with improved efficacy at correcting the metabolic aberrations and motor function deficits in a mouse model of Pompe disease. Mol Ther \n                           17, 954\u2013963, https:\/\/doi.org\/10.1038\/mt.2009.37 (2009).","journal-title":"Mol Ther"},{"key":"15352_CR15","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/mt.2015.62","volume":"23","author":"G Parenti","year":"2015","unstructured":"Parenti, G., Andria, G. & Valenzano, K. J. Pharmacological Chaperone Therapy: Preclinical Development, Clinical Translation, and Prospects for the Treatment of Lysosomal Storage Disorders. 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