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Ganglioside Storage Diseases: On the Road to Management

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Glycobiology of the Nervous System

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 9))

Abstract

Although the biochemical and genetic basis for the GM1 and GM2 gangliosidoses has been known for decades, effective therapies for these diseases remain in early stages of development. The difficulty with many therapeutic strategies for treating the gangliosidoses comes largely from their inability to remove stored ganglioside once it accumulates in central nervous system (CNS) neurons and glia. This chapter highlights advances made using substrate reduction therapy and gene therapy in reducing CNS ganglioside storage. Information obtained from mouse and feline models provides insight on therapeutic strategies that could be effective in human clinical trials. In addition, information is presented showing how a calorie-restricted diet might facilitate therapeutic drug delivery to the CNS. The development of multiple new therapeutic approaches offers hope that longer-term management of these diseases can be achieved. It is also clear that multiple therapeutic strategies will likely be needed to provide the most complete management.

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Abbreviations

6S-NBI-DGJ:

Bicyclic 1-deoxygalactonojirimycin

AAV:

Adeno-associated virus

AL:

Ad libitum

CB:

Cerebroside

CNS:

Central nervous system

CR:

Caloric restriction

GalCer:

Galactosylceramide

GlcCer:

Glucosylceramide

GlcT:

Glucosyltransferase-1

GSL:

Glycosphingolipid

KD-R:

Restricted ketogenic diet

LacCer:

Lactosylceramide

NB-DGJ:

N-butyldeoxygalactonojirimycin

NB-DNJ:

N-butyldeoxynojirimycin

NN-DGJ:

N-nonyl-deoxygalactonojirimycin

PDMP:

d-threo-1-phenyl-2-decanoylamino-3-morpholino-propanol

PNS:

Peripheral nervous system

SD:

Sandhoff disease

SRT:

Substrate reduction therapy

TSD:

Tay-Sachs disease

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Acknowledgements

This work was supported in part by National Institutes of Health Grants R01NS-055195 (TNS), R21NS053993 (MSE), and U01-NS064096 (TNS, DRM, MSE), the Boston College Research Expense Fund, the Scott-Ritchey Research Center, the Lysosomal Storage Disease Research Consortium, and the National Tay-Sachs and Allied Diseases Association, Inc.

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Authors and Affiliations

  1. Biology Department, Boston College, Chestnut Hill, MA, 02467, USA

    Thomas N. Seyfried, Hannah E. Rockwell & Karie A. Heinecke

  2. Scott-Ritchey Research Center and Department of Anatomy, Physiology & Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, 36849, USA

    Douglas R. Martin

  3. Department of Neurology and Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, 01605, USA

    Miguel Sena-Esteves

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Correspondence to Thomas N. Seyfried .

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Editors and Affiliations

  1. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, USA

    Robert K. Yu

  2. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA

    Cara-Lynne Schengrund

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Seyfried, T.N., Rockwell, H.E., Heinecke, K.A., Martin, D.R., Sena-Esteves, M. (2014). Ganglioside Storage Diseases: On the Road to Management. In: Yu, R., Schengrund, CL. (eds) Glycobiology of the Nervous System. Advances in Neurobiology, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1154-7_22

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