title: Advances and pitfalls of cell therapy in metabolic leukodystrophies.
abstract: 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.
authors.affiliation: Nerve Regeneration Group, IBMC-Instituto de Biologia Molecular e Celular, 4150-180 Porto, Portugal.
authors.forename: Catarina Oliveira
authors.initials: CO
authors.lastname: Miranda
authors.forename: Pedro
authors.initials: P
authors.lastname: Brites
authors.forename: Mónica
authors.initials: M
authors.lastname: Mendes Sousa
authors.forename: Carla Andreia
authors.initials: CA
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017690:Cell Transplantation / Q000009:adverse effects / Q000639:trends*; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects / Q000639:trends*; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000503:physiopathology / Q000628:therapy*; D007966:Leukodystrophy, Metachromatic / Q000378:metabolism / Q000473:pathology / Q000628:therapy*