title: Myelin repair by transplantation of myelin-forming cells in globoid cell leukodystrophy.
abstract: Globoid cell leukodystrophy (GLD), or Krabbe disease, is a devastating demyelinating disease that affects both the central and peripheral nervous systems. It is caused by genetic deficiency in the activity of a lysosomal enzyme, galactocerebrosidase (GALC), which is necessary for the maintenance of myelin. Hematopoietic stem cell transplantation (HSCT) including umbilical cord stem cell transplantation is the only effective therapy available to date. HSCT significantly prolongs the life span of patients with GLD when performed before disease onset, although it is not curative. In HSCT, infiltrating donor-derived macrophages are thought to indirectly supply the enzyme (called "cross-correction") to the host's myelinating cells. Given the limitation in treating GLD, it is hypothesized that remyelinating demyelinated axons with GALC-competent myelinating cells by transplantation will result in more stable myelination than endogenous myelin repair supported by GALC cross-correction. Transplantation of myelin-forming cells in a variety of animal models of dysmyelinating and demyelinating disorders suggests that this approach is promising in restoring saltatory conduction and protecting neurons by providing new healthy myelin. However, GLD is one of the most challenging diseases in terms of the aggressiveness of the disease and widespread pathology. Experimental transplantation of myelin-forming cells in the brain of a mouse model of GLD has been only modestly effective to date. Thus, a practical strategy for myelin repair in GLD would be to combine the rapid and widespread cross-correction of GALC by HSCT with the robust, stable myelination provided by transplanted GALC-producing myelin-forming cells. This short review will discuss such possibilities. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka, Japan. konchan@osaka-med.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Duncan
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000209:etiology* / Q000601:surgery*; D004195:Disease Models, Animal; D005698:Galactosylceramidase / Q000172:deficiency / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000150:complications* / Q000235:genetics / Q000601:surgery; D009186:Myelin Sheath / Q000502:physiology*
chemical_list: D005698:Galactosylceramidase
keywords: Krabbe disease; induced pluripotent stem cells; myelin repair; transplantation