Gene therapy for metachromatic leukodystrophy

Jonathan B. Rosenberg, Stephen M. Kaminsky, Patrick Aubourg, Ronald Crystal, Dolan Sondhi

Research output: Contribution to journalReview article

14 Citations (Scopus)


Leukodystrophies (LDs) are rare, often devastating genetic disorders with neurologic symptoms. There are currently no disease-specific therapeutic approaches for these diseases. In this review we use metachromatic leukodystrophy as an example to outline in the brief the therapeutic approaches to MLD that have been tested in animal models and in clinical trials, such as enzyme-replacement therapy, bone marrow/umbilical cord blood transplants, ex vivo transplantation of genetically modified hematopoietic stem cells, and gene therapy. These studies suggest that to be successful the ideal therapy for MLD must provide persistent and high level expression of the deficient gene, arylsulfatase A in the CNS. Gene therapy using adeno-associated viruses is therefore the ideal choice for clinical development as it provides the best balance of potential for efficacy with reduced safety risk. Here we have summarized the published preclinical data from our group and from others that support the use of a gene therapy with AAVrh.10 serotype for clinical development as a treatment for MLD, and as an example of the potential of gene therapy for LDs especially for Krabbe disease, which is the focus of this special issue.

Original languageEnglish
Pages (from-to)1169-1179
Number of pages11
JournalJournal of Neuroscience Research
Issue number11
Publication statusPublished - 1 Nov 2016
Externally publishedYes



  • adeno-associated virus
  • clinical development
  • clinical translation
  • gene therapy
  • metachromatic leukodystrophy

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Rosenberg, J. B., Kaminsky, S. M., Aubourg, P., Crystal, R., & Sondhi, D. (2016). Gene therapy for metachromatic leukodystrophy. Journal of Neuroscience Research, 94(11), 1169-1179.