Abstract
Background
Globoid cell leukodystrophy or Krabbe disease, is a rapidly progressive childhood
lysosomal storage disorder caused by a deficiency in galactocerebrosidase. Galactocerebrosidase
deficiency leads to the accumulation of galactosylsphingosine (psychosine), a cytotoxic
lipid especially damaging to oligodendrocytes and Schwann cells. The progressive loss
of cells involved in myelination results in a dysmyelinating phenotype affecting both
the central and peripheral nervous systems. Current treatment for globoid cell leukodystrophy
is limited to bone marrow or umbilical cord blood transplantation. However, these
therapies are not curative and simply slow the progression of the disease. The Twitcher
mouse is a naturally occurring biochemically faithful model of human globoid cell
leukodystrophy that has been used extensively to study globoid cell leukodystrophy
pathophysiology and experimental treatments. In this review, we present the major
single and combination experimental therapies targeting specific aspects of murine
globoid cell leukodystrophy.
Methods
Literature review and analysis.
Results
The evidence suggests that even with the best available therapies, targeting a single
pathogenic mechanism provides minimal clinical benefit. More recently, combination
therapies have demonstrated the potential to further advance globoid cell leukodystrophy
treatment by synergistically increasing life span. However, such therapies must be
designed and evaluated carefully because not all combination therapies yield such
positive results.
Conclusions
A more complete understanding of the underlying pathophysiology and the interplay
between various therapies holds the key to the discovery of more effective treatments
for globoid cell leukodystrophy.
Keywords
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Article info
Publication history
Published online: August 08, 2014
Identification
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© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
