Lysosomal storage disease: Gene therapy on both sides of the blood-brain barrier

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37 Scopus citations


Most lysosomal storage disorders affect the nervous system as well as other tissues and organs of the body. Previously, the complexities of these diseases, particularly in treating neurologic abnormalities, were too great to surmount. However, based on recent developments there are realistic expectations that effective therapies are coming soon. Gene therapy offers the possibility of affordable, comprehensive treatment associated with these diseases currently not provided by standards of care. With a focus on correction of neurologic disease by systemic gene therapy of mucopolysaccharidoses types I and IIIA, we review some of the major recent advances in viral and non-viral vectors, methods of their delivery and strategies leading to correction of both the nervous and somatic tissues as well as evaluation of functional correction of neurologic manifestations in animal models. We discuss two questions: what systemic gene therapy strategies work best for correction of both somatic and neurologic abnormalities in a lysosomal storage disorder and is there evidence that targeting peripheral tissues (e.g., in the liver) has a future for ameliorating neurologic disease in patients?

Original languageEnglish (US)
Pages (from-to)83-93
Number of pages11
JournalMolecular Genetics and Metabolism
Issue number2
StatePublished - Feb 1 2015

Bibliographical note

Funding Information:
We thank Scott McIvor for helpful suggestions on the manuscript and Bryan Hall for editorial assistance. This work was supported by the National Institutes of Health grants 1R01DK08251 , P01-HD32652 and 2R44HL072539-04 .

Publisher Copyright:
© 2014 The Authors.


  • Behavior
  • CNS
  • Mucopolysaccharidosis
  • Neurologic
  • Sleeping beauty transposon
  • Transcytosis


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