Open AccessConcise Review: Stem Cell‐Based Treatment of Pelizaeus‐Merzbacher Disease
Author(s) -
Osorio M. Joana,
Rowitch David H.,
Tesar Paul,
Wernig Marius,
Windrem Martha S.,
Goldman Steven A.
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2530
Subject(s) - biology , proteolipid protein 1 , leukodystrophy , phenotype , progenitor cell , neural stem cell , stem cell , transplantation , genetics , gene , bioinformatics , myelin , disease , neuroscience , pathology , myelin basic protein , central nervous system , medicine
A bstract 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. S tem C ells 2017;35:311–315