{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:48:53Z","timestamp":1790498933883,"version":"4.1.0"},"reference-count":66,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p>\n                    Adrenomyeloneuropathy (AMN) is a late-onset axonopathy of spinal cord tracts caused by mutations of the ABCD1 gene that encodes adrenoleukodystrophy protein (ALDP), a peroxisomal transporter of very long-chain fatty acids (VLCFA). Disturbed metabolic interaction between oligodendrocytes (OL) and axons is suspected to play a major role in AMN axonopathy. To develop a vector targeting OL, the human ABCD1 gene driven by a short 0.3\u2009kb part of the human myelin-associated glycoprotein (MAG) promoter was packaged into an adeno-associated viral serotype 9 (rAAV9). An intravenous injection of this vector on postnatal day 10 in Abcd1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, a model of AMN, allowed a near normal motor performance to persist for 24 months, while age-matched untreated mice developed major defects of balance and motricity. Three weeks postvector, 50\u201354% of spinal cord white matter OL was expressing human ALDP (hALDP) at the cervical level, and only 6\u20137% after 24 months. In addition, 29\u201332% of cervical spinal cord astrocytes at 3 weeks and 16\u201319% at 24 months also expressed ALDP. C26:0-lysoPC, a sensitive VLCFA marker of AMN, was lower by 41% and 50%, respectively, in the spinal cord and brain of vector-treated compared with untreated mice. In a nonhuman primate, the intrathecal injection of the rAAV9-MAG vector induced abundant ALDP expression at 3 weeks in spinal cord OL (43%, 29%, and 26% at cervical, thoracic, and lumbar levels) and cerebellum OL (35%). In addition, 33\u201341% of spinal cord astrocytes expressed hALDP, and 27% of cerebellar astrocytes. To our knowledge, OL targeting had not been obtained before in primates with other vectors or promoters. The current results thus provide a robust proof-of-concept not only for the gene therapy of AMN but also for other central nervous system diseases, where the targeting of OL with the rAAV9-MAG vector may be of interest.\n                  <\/jats:p>","DOI":"10.1089\/hum.2021.293","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T06:26:23Z","timestamp":1644906383000},"page":"936-949","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Long-Term Disease Prevention with a Gene Therapy Targeting Oligodendrocytes in a Mouse Model of Adrenomyeloneuropathy"],"prefix":"10.1177","volume":"33","author":[{"given":"Yasemin","family":"\u00d6zg\u00fcr-G\u00fcnes","sequence":"first","affiliation":[{"name":"UMR1195 Inserm and University Paris Saclay, Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malha","family":"Chedik","sequence":"additional","affiliation":[{"name":"UMR1195 Inserm and University Paris Saclay, Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Le Stunff","sequence":"additional","affiliation":[{"name":"UMR1195 Inserm and University Paris Saclay, Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire-Ma\u00eblle","family":"Fovet","sequence":"additional","affiliation":[{"name":"MIRCen Institute, CEA, Fontenay-aux-Roses, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-4572","authenticated-orcid":false,"given":"Pierre","family":"Bougn\u00e8res","sequence":"additional","affiliation":[{"name":"UMR1195 Inserm and University Paris Saclay, Le Kremlin-Bic\u00eatre, France."},{"name":"Therapy Design Consulting, Vincennes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/361726a0"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.2.265"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00391.x"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61171"},{"key":"e_1_3_5_6_2","first-page":"109","article-title":"The genetic landscape of X-linked adrenoleukodystrophy, inheritance, mutations, modifier genes, and diagnosis","volume":"8","author":"Wiesinger C","year":"2015","unstructured":"Wiesinger C, , Eichler FS, , Berger J. The genetic landscape of X-linked adrenoleukodystrophy, inheritance, mutations, modifier genes, and diagnosis. Appl Clin Genet, 2015; 8:109\u2013121.","journal-title":"Appl Clin Genet"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.03.012"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-51"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy299"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/59.2.89"},{"key":"e_1_3_5_11_2","article-title":"Unmasking adrenoleukodystrophy in a cohort of cerebellar ataxia","volume":"12","author":"Chen YC","year":"2017","unstructured":"Chen YC, , Lee YC, , Tsai YS, et al. Unmasking adrenoleukodystrophy in a cohort of cerebellar ataxia. PLoS One, 2017; 12:e0177296.","journal-title":"PLoS One"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt361"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001074"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199006283222607"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.09.036"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1171242"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1700554"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306431101"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2021.053"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9797-1"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.499"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.6"},{"key":"e_1_3_5_23_2","first-page":"S155","article-title":"Impact of rAAV9-ABCD1 upon behavioral outcome in a mouse model of X-ALD","volume":"23","author":"Gong YI MD","year":"2015","unstructured":"Gong YI MD, , Ren J, , Moser A, et al. Impact of rAAV9-ABCD1 upon behavioral outcome in a mouse model of X-ALD. Neurolog Dis, 2015; 23:S155.","journal-title":"Neurolog Dis"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2018.079"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.01.009"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.01.006"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2797"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000621"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.07.007"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2013.09.020"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00467"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.03.058"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx249"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2016.00013"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05765-6"},{"key":"e_1_3_5_36_2","first-page":"2376","article-title":"Assessment of motor balance in mice using the balance beam","volume":"23","author":"Luong TN","year":"2011","unstructured":"Luong TN, , Carlisle HJ, , Southwell A, et al. Assessment of motor balance in mice using the balance beam. Jove, 2011; 23:2376\u20132378.","journal-title":"Jove"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2018.00008"},{"key":"e_1_3_5_38_2","first-page":"1","article-title":"Transcriptome profiling of the Olig2-expressing astrocyte subtype reveals their unique molecular signature","volume":"7","author":"Ohayon D","year":"2021","unstructured":"Ohayon D, , Aguirrebengoa M, , Escalas N, et al. Transcriptome profiling of the Olig2-expressing astrocyte subtype reveals their unique molecular signature. iScience, 2021; 7:1\u201325.","journal-title":"iScience"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-021-00747-0"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4178-07.2008"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154597"},{"key":"e_1_3_5_42_2","article-title":"Oligodendrocytes: myelination and axonal support","volume":"8","author":"Simons M","year":"2015","unstructured":"Simons M, , Nave KA. Oligodendrocytes: myelination and axonal support. Cold Spring Harb Perspect Biol, 2015; 8:a020479.","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1515"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.71"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.72"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2014.32"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2016.81"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2017.18"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.04.001"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.157"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2012.101"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2011.200"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2013.005"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2014.16"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.026"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2016.62"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2021.012"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.146832"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0012-9"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2016.087"},{"key":"e_1_3_5_61_2","first-page":"599","article-title":"Gene therapy targeting oligodendrocytes provides therapeutic benefit in a leukodystrophy model","volume":"140","author":"Georgiou E","year":"2017","unstructured":"Georgiou E, , Sidiropoulou K, , Richter J, et al. Gene therapy targeting oligodendrocytes provides therapeutic benefit in a leukodystrophy model. Brain, 2017; 140:599\u2013616.","journal-title":"Brain"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.01.006"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.011"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijns7030058"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2070"},{"key":"e_1_3_5_66_2","first-page":"71","article-title":"Oligodendrocyte, astrocyte, and microglia crosstalk in myelin development, damage, and repair","volume":"4","author":"Domingues HS","year":"2016","unstructured":"Domingues HS, , Portugal CC, , Socodato R, et al. Oligodendrocyte, astrocyte, and microglia crosstalk in myelin development, damage, and repair. Front Cell Dev Biol, 2016; 4:71.","journal-title":"Front Cell Dev Biol"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0388-4"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2021.293","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2021.293","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2021.293","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T11:57:20Z","timestamp":1773230240000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2021.293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":66,"journal-issue":{"issue":"17-18","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1089\/hum.2021.293"],"URL":"https:\/\/doi.org\/10.1089\/hum.2021.293","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9]]}}}