Concise Review: Stem Cell-Based Treatment of Pelizaeus-Merzbacher Disease

TY - JOUR

T1 - Concise Review

T2 - Stem Cell-Based Treatment of Pelizaeus-Merzbacher Disease

AU - Osorio, M. Joana

AU - Rowitch, David H.

AU - Tesar, Paul

AU - Wernig, Marius

AU - Windrem, Martha S.

AU - Goldman, Steven A.

N1 - © 2016 AlphaMed Press.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

KW - Journal Article

KW - Review

U2 - 10.1002/stem.2530

DO - 10.1002/stem.2530

M3 - Review

C2 - 27882623

SN - 1066-5099

VL - 35

SP - 311

EP - 315

JO - Stem Cells

JF - Stem Cells

IS - 2

ER -