title: Concise Review: Stem Cell-Based Treatment of Pelizaeus-Merzbacher Disease.
abstract: Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder caused by mutation in the proteolipid protein-1 (PLP1) gene, which encodes the proteolipid protein of myelinating oligodendroglia. PMD exhibits phenotypic variability that reflects its considerable genotypic heterogeneity, but all forms of the disease result in central hypomyelination, associated in most cases with early neurological dysfunction, progressive deterioration, and ultimately death. PMD may present as a connatal, classic and transitional forms, or as the less severe spastic paraplegia type 2 and PLP-null phenotypes. These disorders are most often associated with duplications of the PLP1 gene, but can also be caused by coding and noncoding point mutations as well as full or partial deletion of the gene. A number of genetically-distinct but phenotypically-similar disorders of hypomyelination exist which, like PMD, lack any effective therapy. Yet as relatively pure CNS hypomyelinating disorders, with limited involvement of the PNS and relatively little attendant neuronal pathology, PMD and similar hypomyelinating disorders are attractive therapeutic targets for neural stem cell and glial progenitor cell transplantation, efforts at which are now underway in a number of research centers. Stem Cells 2017;35:311-315.
authors.affiliation: Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M Joana
authors.initials: MJ
authors.lastname: Osorio
authors.affiliation: Departments of Pediatrics and Neurosurgery, UCSF School of Medicine and Broad Center for Regenerative Medicine, San Francisco, California, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Tesar
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine.|Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Marius
authors.initials: M
authors.lastname: Wernig
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Martha S
authors.initials: MS
authors.lastname: Windrem
authors.affiliation: Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark.|Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism; D020371:Pelizaeus-Merzbacher Disease / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
keywords: Cell transplantation; Glia; Hypomyelinating disorders; Leukodystrophy; Neural stem cells; Oligodendrocytes; Pelizaeus-Merzbacher disease; Proteolipid protein-1; Stem cells