TY - JOUR
T1 - Cellular transplant therapies for globoid cell leukodystrophy
T2 - Preclinical and clinical observations
AU - Maher, Keri R.
AU - Yeager, Andrew M.
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Globoid cell leukodystrophy (GLD) is a progressive neurodegenerative disorder caused by the deficiency of galactocerebrosidase (GALC), resulting in accumulation of toxic metabolites in neural tissues. Clinically variable based on age of onset, infantile GLD is generally a rapidly fatal syndrome of progressive neurologic and cognitive decline, whereas later-onset GLD has a more indolent, protracted clinical course. Animal models, particularly the twitcher mouse, have allowed investigation of both the pathophysiology of and the potential treatment modalities for GLD. Cellular therapy for GLD, notably hematopoietic cell transplantation (HCT; transplantation of bone marrow, peripheral blood stem cells, or umbilical cord blood cells) from a normal related or unrelated allogeneic donor provides a self-renewing source of GALC in donor-derived cells. The only currently available treatment option in human GLD, allogeneic HCT, can slow the progression of the disease and improve survival, especially when performed in presymptomatic infants. Because persistent neurologic dysfunction still occurs after HCT in GLD, preclinical studies are evaluating combinations of HCT with other treatment modalities.
AB - Globoid cell leukodystrophy (GLD) is a progressive neurodegenerative disorder caused by the deficiency of galactocerebrosidase (GALC), resulting in accumulation of toxic metabolites in neural tissues. Clinically variable based on age of onset, infantile GLD is generally a rapidly fatal syndrome of progressive neurologic and cognitive decline, whereas later-onset GLD has a more indolent, protracted clinical course. Animal models, particularly the twitcher mouse, have allowed investigation of both the pathophysiology of and the potential treatment modalities for GLD. Cellular therapy for GLD, notably hematopoietic cell transplantation (HCT; transplantation of bone marrow, peripheral blood stem cells, or umbilical cord blood cells) from a normal related or unrelated allogeneic donor provides a self-renewing source of GALC in donor-derived cells. The only currently available treatment option in human GLD, allogeneic HCT, can slow the progression of the disease and improve survival, especially when performed in presymptomatic infants. Because persistent neurologic dysfunction still occurs after HCT in GLD, preclinical studies are evaluating combinations of HCT with other treatment modalities.
KW - GALC
KW - Krabbe's disease
KW - galactocerebrosidase
KW - globoid cell leukodystrophy
KW - hematopoietic cell transplantation
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U2 - 10.1002/jnr.23782
DO - 10.1002/jnr.23782
M3 - Review article
C2 - 27638602
AN - SCOPUS:84990252375
SN - 0360-4012
VL - 94
SP - 1180
EP - 1188
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 11
ER -