AAV Gene Therapy Strategies for Lysosomal Storage Disorders with Central Nervous System Involvement

  • Diane Golebiowski
  • Allison M. Bradbury
  • Churl-Su Kwon
  • Imramsjah M. J. van der Bom
  • Lorelei Stoica
  • Aime K. Johnson
  • Diane U. Wilson
  • Heather L. Gray-Edwards
  • Judith A. Hudson
  • Jacob A. Johnson
  • Ashley N. Randle
  • Brian K. Whitlock
  • James L. Sartin
  • Anna Luisa Kühn
  • Matthew Gounis
  • Wael Asaad
  • Douglas R. Martin
  • Miguel Sena-EstevesEmail author
Part of the Neuromethods book series (NM, volume 98)


Gene therapy is one of the most promising approaches for the treatment of lysosomal storage disorders (LSDs). This is especially true for the 75 % of LSDs that have central nervous system (CNS) involvement, where enzyme replacement therapy (ERT), the standard of care for LSDs, is ineffective in treating the neurological features of these diseases. Recombinant adeno-associated virus (AAV) vectors have emerged as the most efficient and promising gene transfer vehicles for the CNS and in particular for LSDs. Direct infusion of AAV vectors into interconnected structures in the brain has achieved widespread distribution of vector and therapeutic levels of lysosomal enzymes throughout the CNS. Early stages of clinical trials are currently underway for treating neurological disorders with AAV vectors, with much anticipation for moving these treatments forward to aid patients and families affected by these terrible diseases. In this chapter, we will detail the protocols used for stereotaxic AAV infusion into the brain of mice, cats, sheep, and nonhuman primates.

Key words

Gene therapy Lysosomal storage disorders Stereotaxic brain injections Mouse Cat Sheep Nonhuman primate 


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Diane Golebiowski
    • 1
    • 2
  • Allison M. Bradbury
    • 3
  • Churl-Su Kwon
    • 4
  • Imramsjah M. J. van der Bom
    • 5
    • 6
  • Lorelei Stoica
    • 1
    • 2
  • Aime K. Johnson
    • 7
  • Diane U. Wilson
    • 3
  • Heather L. Gray-Edwards
    • 3
  • Judith A. Hudson
    • 7
  • Jacob A. Johnson
    • 7
  • Ashley N. Randle
    • 3
  • Brian K. Whitlock
    • 8
  • James L. Sartin
    • 9
  • Anna Luisa Kühn
    • 5
    • 6
  • Matthew Gounis
    • 5
    • 6
  • Wael Asaad
    • 10
  • Douglas R. Martin
    • 3
    • 9
  • Miguel Sena-Esteves
    • 1
    • 2
    Email author
  1. 1.Departments of NeurologyUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Gene Therapy CenterUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.Scott-Ritchey Research Center, College of Veterinary MedicineAuburn UniversityAuburnUSA
  4. 4.Department of NeurosurgeryMassachusetts General HospitalBostonUSA
  5. 5.Department of RadiologyUniversity of Massachusetts Medical SchoolWorcesterUSA
  6. 6.New England Center for Stroke ResearchUniversity of Massachusetts Medical SchoolWorcesterUSA
  7. 7.Department of Clinical Sciences, College of Veterinary MedicineAuburn UniversityAuburnUSA
  8. 8.Department of Large Animal Clinical SciencesUniversity of Tennessee College of Veterinary MedicineKnoxvilleUSA
  9. 9.Department of Anatomy, Physiology & Pharmacology, College of Veterinary MedicineAuburn UniversityAuburnUSA
  10. 10.Department of Neurosurgery and Brown Institute for Brain ScienceBrown University Alpert Medical School and Rhode Island HospitalProvidenceUSA

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