Advances and Pitfalls of Cell Therapy in Metabolic Leukodystrophies
Leukodystrophies are a group of disorders characterized by myelin dysfunction, either at the level of myelin formation or maintenance, that affect the central nervous system (CNS) and also in some cases, to a lesser extent, the peripheral nervous system (PNS). Although these genetic-based disorders...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2013-02-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X656117 |
| _version_ | 1818576770731868160 |
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| author | Catarina Oliveira Miranda Pedro Brites Mónica Mendes Sousa Carla Andreia Teixeira |
| author_facet | Catarina Oliveira Miranda Pedro Brites Mónica Mendes Sousa Carla Andreia Teixeira |
| author_sort | Catarina Oliveira Miranda |
| collection | DOAJ |
| description | Leukodystrophies are a group of disorders characterized by myelin dysfunction, either at the level of myelin formation or maintenance, that affect the central nervous system (CNS) and also in some cases, to a lesser extent, the peripheral nervous system (PNS). Although these genetic-based disorders are generally rare, all together they have a significant impact in the society, with an estimated overall incidence of 1 in 7,663 live births. Currently, there is no cure for leukodystrophies, and the development of effective treatments remains challenging. Not only leukodystrophies generally progress very fast, but also most are multifocal needing the simultaneous targeting at multiple sites. Moreover, as the CNS is affected, the blood–brain barrier (BBB) limits the efficacy of treatment. Recently, interest on cell therapy has increased, and the leukodystrophies for which metabolic correction is needed have become first-choice candidates for cell-based clinical trials. In this review, we present and discuss the available cell transplantation therapies in metabolic leukodystrophies including fucosidosis, X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Canavan disease, and Krabbe's disease. We will discuss the latest advances of cell therapy and its pitfalls in this group of disorders, taking into account, among others, the limitations imposed by reduced cell migration in multifocal conditions, the need to achieve corrective enzyme threshold levels, and the growing awareness that not only myelin but also the associated axonopathy needs to be targeted in some leukodystrophies. |
| first_indexed | 2024-12-16T06:19:18Z |
| format | Article |
| id | doaj.art-addfbe0ff0264b759152371e3598bc0b |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-16T06:19:18Z |
| publishDate | 2013-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-addfbe0ff0264b759152371e3598bc0b2022-12-21T22:41:10ZengSAGE PublishingCell Transplantation0963-68971555-38922013-02-012210.3727/096368912X656117Advances and Pitfalls of Cell Therapy in Metabolic LeukodystrophiesCatarina Oliveira Miranda0Pedro Brites1Mónica Mendes Sousa2Carla Andreia Teixeira3ICBAS, Universidade do Porto, Porto, PortugalNerve Regeneration Group, IBMC-Instituto de Biologia Molecular e Celular, Porto, PortugalNerve Regeneration Group, IBMC-Instituto de Biologia Molecular e Celular, Porto, PortugalNerve Regeneration Group, IBMC-Instituto de Biologia Molecular e Celular, Porto, PortugalLeukodystrophies are a group of disorders characterized by myelin dysfunction, either at the level of myelin formation or maintenance, that affect the central nervous system (CNS) and also in some cases, to a lesser extent, the peripheral nervous system (PNS). Although these genetic-based disorders are generally rare, all together they have a significant impact in the society, with an estimated overall incidence of 1 in 7,663 live births. Currently, there is no cure for leukodystrophies, and the development of effective treatments remains challenging. Not only leukodystrophies generally progress very fast, but also most are multifocal needing the simultaneous targeting at multiple sites. Moreover, as the CNS is affected, the blood–brain barrier (BBB) limits the efficacy of treatment. Recently, interest on cell therapy has increased, and the leukodystrophies for which metabolic correction is needed have become first-choice candidates for cell-based clinical trials. In this review, we present and discuss the available cell transplantation therapies in metabolic leukodystrophies including fucosidosis, X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Canavan disease, and Krabbe's disease. We will discuss the latest advances of cell therapy and its pitfalls in this group of disorders, taking into account, among others, the limitations imposed by reduced cell migration in multifocal conditions, the need to achieve corrective enzyme threshold levels, and the growing awareness that not only myelin but also the associated axonopathy needs to be targeted in some leukodystrophies.https://doi.org/10.3727/096368912X656117 |
| spellingShingle | Catarina Oliveira Miranda Pedro Brites Mónica Mendes Sousa Carla Andreia Teixeira Advances and Pitfalls of Cell Therapy in Metabolic Leukodystrophies Cell Transplantation |
| title | Advances and Pitfalls of Cell Therapy in Metabolic Leukodystrophies |
| title_full | Advances and Pitfalls of Cell Therapy in Metabolic Leukodystrophies |
| title_fullStr | Advances and Pitfalls of Cell Therapy in Metabolic Leukodystrophies |
| title_full_unstemmed | Advances and Pitfalls of Cell Therapy in Metabolic Leukodystrophies |
| title_short | Advances and Pitfalls of Cell Therapy in Metabolic Leukodystrophies |
| title_sort | advances and pitfalls of cell therapy in metabolic leukodystrophies |
| url | https://doi.org/10.3727/096368912X656117 |
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