{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:45:37Z","timestamp":1789764337588,"version":"4.0.1"},"reference-count":160,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hacettepe University Scientific Research Project Coordination Unit","award":["TAY-2022-20436"],"award-info":[{"award-number":["TAY-2022-20436"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Leukodystrophies are a heterogenous group of inherited, degenerative encephalopathies, that if left untreated, are often lethal at an early age. Although some of the leukodystrophies can be treated with allogeneic hematopoietic stem cell transplantation, not all patients have suitable donors, and new treatment strategies, such as gene therapy, are rapidly being developed. Recent developments in the field of gene therapy for severe combined immune deficiencies, Leber\u2019s amaurosis, epidermolysis bullosa, Duchenne\u2019s muscular dystrophy and spinal muscular atrophy, have paved the way for the treatment of leukodystrophies, revealing some of the pitfalls, but overall showing promising results. Gene therapy offers the possibility for overexpression of secretable enzymes that can be released and through uptake, allow cross-correction of affected cells. Here, we discuss some of the leukodystrophies that have demonstrated strong potential for gene therapy interventions, such as X-linked adrenoleukodystrophy (X-ALD), and metachromatic leukodystrophy (MLD), which have reached clinical application. We further discuss the advantages and disadvantages of ex vivo lentiviral hematopoietic stem cell gene therapy, an approach for targeting microglia-like cells or rendering cross-correction. In addition, we summarize ongoing developments in the field of in vivo administration of recombinant adeno-associated viral (rAAV) vectors, which can be used for direct targeting of affected cells, and other recently developed molecular technologies that may be applicable to treating leukodystrophies in the future.<\/jats:p>","DOI":"10.3390\/pharmaceutics15112522","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T06:29:01Z","timestamp":1698128941000},"page":"2522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gene and Cellular Therapies for Leukodystrophies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9583-8572","authenticated-orcid":false,"given":"Fatima","family":"Aerts-Kaya","sequence":"first","affiliation":[{"name":"Department of Stem Cell Sciences, Graduate School of Health Sciences, Center for Stem Cell Research and Development, Hacettepe University, 06100 Ankara, Turkey"},{"name":"Advanced Technologies Application and Research Center, Hacettepe University, 06800 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-4103","authenticated-orcid":false,"given":"Niek P.","family":"van Til","sequence":"additional","affiliation":[{"name":"Amsterdam Leukodystrophy Center, Emma Children\u2019s Hospital, Amsterdam University Medical Centers, Amsterdam Neuroscience, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00401-017-1739-1","article-title":"Leukodystrophies: A proposed classification system based on pathological changes and pathogenetic mechanisms","volume":"134","author":"Bugiani","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101312","DOI":"10.1016\/j.cppeds.2022.101312","article-title":"Introduction to leukodystrophy","volume":"52","author":"Shin","year":"2022","journal-title":"Curr. 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