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

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Gene Delivery and Therapy for Neurological Disorders

Part of the book series: Neuromethods ((NM,volume 98))

Abstract

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.

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Authors and Affiliations

  1. Departments of Neurology, University of Massachusetts Medical School, 381 Plantation Street, Worcester, MA, 01605, USA

    Diane Golebiowski, Lorelei Stoica & Miguel Sena-Esteves

  2. Gene Therapy Center, University of Massachusetts Medical School, 381 Plantation Street, Worcester, MA, 01605, USA

    Diane Golebiowski, Lorelei Stoica & Miguel Sena-Esteves

  3. Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA

    Allison M. Bradbury, Diane U. Wilson, Heather L. Gray-Edwards, Ashley N. Randle & Douglas R. Martin

  4. Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA

    Churl-Su Kwon

  5. Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA

    Imramsjah M. J. van der Bom, Anna Luisa Kühn & Matthew Gounis

  6. New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, MA, USA

    Imramsjah M. J. van der Bom, Anna Luisa Kühn & Matthew Gounis

  7. Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, USA

    Aime K. Johnson, Judith A. Hudson & Jacob A. Johnson

  8. Department of Large Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, TN, USA

    Brian K. Whitlock

  9. Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA

    James L. Sartin & Douglas R. Martin

  10. Department of Neurosurgery and Brown Institute for Brain Science, Brown University Alpert Medical School and Rhode Island Hospital, Providence, RI, USA

    Wael Asaad

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  1. Diane Golebiowski
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  2. Allison M. Bradbury
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  7. Diane U. Wilson
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  16. Wael Asaad
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  17. Douglas R. Martin
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  18. Miguel Sena-Esteves
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Corresponding author

Correspondence to Miguel Sena-Esteves .

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Editors and Affiliations

  1. Queen Mary University of London, London, United Kingdom

    Xuenong Bo

  2. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

    Joost Verhaagen

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Golebiowski, D. et al. (2015). AAV Gene Therapy Strategies for Lysosomal Storage Disorders with Central Nervous System Involvement. In: Bo, X., Verhaagen, J. (eds) Gene Delivery and Therapy for Neurological Disorders. Neuromethods, vol 98. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2306-9_11

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  • DOI: https://doi.org/10.1007/978-1-4939-2306-9_11

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2305-2

  • Online ISBN: 978-1-4939-2306-9

  • eBook Packages: Springer Protocols

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