Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease

Steven U. Walkley, M. A. Thrall, Kostantin Dobrenis, M. Huang, P. A. March, D. A. Siegel, S. Wurzelmann

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Neuronal storage disorders are fatal neurodegenerative diseases of humans and animals that are caused by inherited deficiencies of lysosomal hydrolase activity. Affected individuals often appear normal at birth but eventually develop progressive neurologic symptoms including sensory and motor deficits, mental retardation, and seizures. We have examined efficacy of bone marrow transplantation as a means of enzyme replacement, using cats with the lysosomal storage disease α-mannosidosis. Treated animals showed little or no progression of neurologic signs 1-2 years after transplant, whereas untreated cats became severely impaired and reached end-stage disease by 6 months of age. Increased lysosomal α-mannosidase activity was found in brain tissue of the treated animals, and electron microscopy revealed no evidence of lysosomal storage within most neurons. Histochemical localization of acidic α-D-mannoside mannohydrolase (EC 3.2. 1.24), using 5-bromo-4-chloro- 3-indolyl α-D-mannopyranoside, showed that functional enzyme was present in neurons, glial cells, and cells associated with blood vessels. This study provides direct evidence that bone marrow transplantation as treatment for a neuronal storage disease can lead to significant levels of a missing lysosomal hydrolase within neurons of the central nervous system and to compensation for the genetic metabolic defect.

Original languageEnglish (US)
Pages (from-to)2970-2974
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number8
StatePublished - Apr 12 1994

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Lysosomal Storage Diseases
Bone Marrow Transplantation
Central Nervous System
Hydrolases
Neurologic Manifestations
Neurons
Mannosidase Deficiency Diseases
Cats
Enzymes
Mannosidases
Mannosides
Mannose
Neuroglia
Intellectual Disability
Neurodegenerative Diseases
Blood Vessels
Electron Microscopy
Seizures
Parturition
Transplants

Keywords

  • α-mannosidosis
  • genetic disease
  • lysosomal enzyme

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease. / Walkley, Steven U.; Thrall, M. A.; Dobrenis, Kostantin; Huang, M.; March, P. A.; Siegel, D. A.; Wurzelmann, S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 8, 12.04.1994, p. 2970-2974.

Research output: Contribution to journalArticle

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