Experimental therapies in the murine model of globoid cell leukodystrophy

Yedda Li, Mark S. Sands

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


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.

Original languageEnglish
Pages (from-to)600-606
Number of pages7
JournalPediatric Neurology
Issue number5
StatePublished - Nov 1 2014


  • Krabbe disease
  • bone marrow transplantation
  • galactocerebrosidase
  • gene therapy
  • globoid cell leukodystrophy
  • lysosomal storage disease

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