UMMS Affiliation

Horae Gene Therapy Center; Department of Microbiology and Physiological Systems; Li Weibo Institute for Rare Diseases Research

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Document Type



Cell Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetics and Genomics | Molecular and Cellular Neuroscience | Nervous System Diseases


In recent years, the scientific and therapeutic fields for rare, genetic central nervous system (CNS) diseases such as leukodystrophies, or white matter disorders, have expanded significantly in part due to technological advancements in cellular and clinical screenings as well as remedial therapies using novel techniques such as gene therapy. However, treatments aimed at normalizing the pathological changes associated with leukodystrophies have especially been complicated due to the innate and variable effects of glial abnormalities, which can cause large-scale functional deficits in developmental myelination and thus lead to downstream neuronal impairment. Emerging research in the past two decades have depicted glial cells, particularly oligodendrocytes and astrocytes, as key, regulatory modulators in constructing and maintaining myelin function and neuronal viability. Given the significance of myelin formation in the developing brain, myelin repair in a time-dependent fashion is critical in restoring homeostatic functionality to the CNS of patients diagnosed with white matter disorders. Using Canavan Disease (CD) as a leukodystrophy model, here we review the hypothetical roles of N-acetylaspartate (NAA), one of the brain's most abundant amino acid derivatives, in Canavan disease's CNS myelinating pathology, as well as discuss the possible functions astrocytes serve in both CD and other leukodystrophies' time-sensitive disease correction. Through this analysis, we also highlight the potential remyelinating benefits of gene therapy for other leukodystrophies in which alternative CNS cell targeting for white matter disorders may be an applicable path for reparative treatment.


Canavan disease, NAA, astrocyte, gene therapy, leukodystrophy, myelination, oligodendrocyte, white matter

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Copyright © 2021 Lotun, Gessler and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version



Lotun A, Gessler DJ, Gao G. Canavan Disease as a Model for Gene Therapy-Mediated Myelin Repair. Front Cell Neurosci. 2021 Apr 23;15:661928. doi: 10.3389/fncel.2021.661928. PMID: 33967698; PMCID: PMC8102781. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in cellular neuroscience

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.