Stem cell and gene therapies for leukodystrophies

Leukodystrophies form a group of rare genetic disorders characterized by the progressive degeneration of white matter in the brain, often presenting in childhood with life-threatening consequences. Current therapeutic options are limited, particularly after symptom onset, and delayed diagnosis exace...

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Bibliographic Details
Main Authors: Wenhao Lin, Min Zhang, Sirui Zheng, Qizhou Lian
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Molecular Therapy: Methods & Clinical Development
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Online Access:http://www.sciencedirect.com/science/article/pii/S2329050125001226
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Summary:Leukodystrophies form a group of rare genetic disorders characterized by the progressive degeneration of white matter in the brain, often presenting in childhood with life-threatening consequences. Current therapeutic options are limited, particularly after symptom onset, and delayed diagnosis exacerbates disease progression. Stem cell and gene therapies have emerged as promising strategies to address these challenges. Neural stem cells (NSCs) and hematopoietic stem cells (HSCs) offer potential for CNS repair through differentiation into neurons and/or glial cells. Human pluripotent stem cells (hPSCs) provide a valuable model for studying disease mechanisms, drug screening, and therapeutic development. Additionally, mesenchymal stem cells (MSCs) exhibit immunomodulatory and secretory properties that may confer therapeutic benefits. Advanced gene therapies, including stem cell-based gene therapy and adeno-associated virus (AAV)-mediated gene replacement therapy (GRT), hold promise for curative interventions. This review highlights recent advances and challenges in stem cell and gene therapies for leukodystrophies, proposing a strategic integration of these approaches to maximize therapeutic efficacy by addressing their respective strengths and limitations.
ISSN:2329-0501