TY - JOUR
T1 - Immunological considerations for treating globoid cell leukodystrophy
AU - Karumuthil-Melethil, Subha
AU - Gray, Steven J.
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Globoid cell leukodystrophy (GLD, or Krabbe's disease) is a severe inherited neurodegenerative disease caused by the lack of a lysosomal enzyme, GALC. The disease has been characterized in humans as well as three naturally occurring animal models, murine, canine, and nonhuman primate. Multiple treatment strategies have been explored for GLD, including enzyme replacement therapy, small-molecule pharmacological approaches, gene therapy, and bone marrow transplant. No single therapeutic approach has proved to be entirely effective, and the reason for this is not well understood. It is unclear whether initiation of a neuroinflammatory cascade in GLD precedes demyelination, a hallmark of the disease, but it does precede overt symptoms. This Review explores what is known about the role of inflammation and the immune response in the progression of GLD as well as how various treatment strategies might interplay with innate and adaptive immune responses involved in GLD. The focus of this Review is on GLD, but these concepts may have relevance for other, related diseases.
AB - Globoid cell leukodystrophy (GLD, or Krabbe's disease) is a severe inherited neurodegenerative disease caused by the lack of a lysosomal enzyme, GALC. The disease has been characterized in humans as well as three naturally occurring animal models, murine, canine, and nonhuman primate. Multiple treatment strategies have been explored for GLD, including enzyme replacement therapy, small-molecule pharmacological approaches, gene therapy, and bone marrow transplant. No single therapeutic approach has proved to be entirely effective, and the reason for this is not well understood. It is unclear whether initiation of a neuroinflammatory cascade in GLD precedes demyelination, a hallmark of the disease, but it does precede overt symptoms. This Review explores what is known about the role of inflammation and the immune response in the progression of GLD as well as how various treatment strategies might interplay with innate and adaptive immune responses involved in GLD. The focus of this Review is on GLD, but these concepts may have relevance for other, related diseases.
KW - GALC
KW - Krabbe's disease
KW - globoid cell leukodystrophy
KW - immune
KW - neuroinflammation
KW - psychosine
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U2 - 10.1002/jnr.23874
DO - 10.1002/jnr.23874
M3 - Review article
C2 - 27638617
AN - SCOPUS:84990244457
SN - 0360-4012
VL - 94
SP - 1349
EP - 1358
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 11
ER -