{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:03:55Z","timestamp":1792047835756,"version":"4.4.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"19-20","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"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":[[2021,10]]},"abstract":"<jats:p>\n                    In 2009, cerebral adrenoleukodystrophy (c-ALD) became the first brain disease to be treated with lentiviral (LV)-based hematopoietic stem cell gene therapy with the\n                    <jats:italic toggle=\"yes\">ABCD1<\/jats:italic>\n                    gene in four boys (P1\u2013P4) who had demyelinating lesions expected to be lethal in the short term and no bone marrow donor. We report the clinical and magnetic resonance imaging (MRI) follow-up over a mean of 8.8 years posttransplant. In parallel, vector genome copies, expression of transgenic ALD protein (ALDP), and viral integration sites were determined in peripheral blood cells. Prior to transplant, the four patients had a normal or near normal neurocognitive status but gadolinium-enhanced demyelination in various brain regions. Gadolinium diffusion disappeared during the first year posttransplant. P3 kept a near normal status until 8.3 years of follow-up, but P1, P2, and P4 showed major cognitive degradation around 9, 28, and 60 months posttransplant. Neurological status and demyelination stabilized until last evaluation in P2, but deteriorated in both P1 at 10 years and P4 at 3 years posttransplant. The proportion of myeloid and lymphoid cells expressing transgenic ALDP decreased by half within 5 years then stabilized around 5% to 10%. Integration site analysis revealed a durable polyclonal distribution of genetically corrected hematopoietic cells. No adverse effects were observed. The long-term arrest of demyelination at MRI and persistence of transduced hematopoietic progenitors support that LV gene therapy may be a safe and durable treatment of c-ALD. However, the neurological degradation observed in three out of four patients mitigates the benefit of this therapy, calling for an earlier intervention, more potent vectors, and additional therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1089\/hum.2021.053","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T03:43:02Z","timestamp":1617248582000},"page":"1260-1269","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":43,"title":["Long-Term Follow-Up of Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-4572","authenticated-orcid":false,"given":"Pierre","family":"Bougn\u00e8res","sequence":"first","affiliation":[{"name":"UMR1195 INSERM, Le Kremlin Bic\u00eatre, France"},{"name":"Universit\u00e9 Paris Saclay, MIRCen Institute\/Neuratris, Fontenay-aux-Roses, France"},{"name":"Therapy Design Consulting, Vincennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salima","family":"Hacein-Bey-Abina","sequence":"additional","affiliation":[{"name":"Clinical Immunology Laboratory, H\u00f4pital Kremlin-Bic\u00eatre, Assistance Publique-H\u00f4pitaux de Paris, Universit\u00e9 Paris Saclay, Paris, France"},{"name":"UTCBS, CNRS UMR8258, INSERM U1267, Facult\u00e9 de Pharmacie de Paris, Universit\u00e9 de Paris, Le Kremlin-Bic\u00eatre, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Labik","sequence":"additional","affiliation":[{"name":"GeneWerk GmbH, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Adamsbaum","sequence":"additional","affiliation":[{"name":"Pediatric Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-4286","authenticated-orcid":false,"given":"Cl\u00e9mence","family":"Castaign\u00e8de","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, H\u00f4pital Kremlin-Bic\u00eatre, Assistance Publique-H\u00f4pitaux de Paris, Universit\u00e9 Paris Saclay, Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5733-711X","authenticated-orcid":false,"given":"C\u00e9line","family":"Bellesme","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, H\u00f4pital Kremlin-Bic\u00eatre, Assistance Publique-H\u00f4pitaux de Paris, Universit\u00e9 Paris Saclay, Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Schmidt","sequence":"additional","affiliation":[{"name":"GeneWerk GmbH, Heidelberg, 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