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Ganglioside Storage Diseases: On the Road to Management

  • Thomas N. Seyfried
  • Hannah E. Rockwell
  • Karie A. Heinecke
  • Douglas R. Martin
  • Miguel Sena-Esteves
Chapter
Part of the Advances in Neurobiology book series (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.

Keywords

GM1 GM2 Sandhoff disease • Tay-Sachs disease Imino sugar Gene therapy Adeno-associated virus (AAV) Calorie restriction Ketogenic diet 

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

Notes

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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Thomas N. Seyfried
    • 1
  • Hannah E. Rockwell
    • 1
  • Karie A. Heinecke
    • 1
  • Douglas R. Martin
    • 2
  • Miguel Sena-Esteves
    • 3
  1. 1.Biology DepartmentBoston CollegeChestnut HillUSA
  2. 2.Scott-Ritchey Research Center and Department of Anatomy, Physiology & PharmacologyAuburn University College of Veterinary MedicineAuburnUSA
  3. 3.Department of Neurology and Gene Therapy CenterUniversity of Massachusetts Medical SchoolWorcesterUSA

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