Lysosomal Storage Disorders pp 197-216
Neural Stem Cell Therapy in Lysosomal Storage Disorders
Many lysosomal storage disorders (LSDs) produce neurodegeneration as a prominent feature (Neufeld, 1991). LSDs are autosomal recessive metabolic diseases caused by deficiencies of specific acid hydrolases resulting in accumulation of unmetabolized substrates and macromolecules in lysosomes. There are ~50 diseases that can be classified as LSDs. The precise mechanisms underlying the actual neurodegenerative process remain to be determined, however, it is known that replacement of the absent gene product typically restores normal metabolism to a cell including forestalling neural cell dysfunction, at least in vitro. Nevertheless, there are currently no effective treatments for the neurological manifestations of the infantile-onset forms of the LSDs. The neuropathology of LSDs is characterized not by discrete focal neuropathology, as in Parkinson’s disease, but rather by extensive, multifocal, or even “global” neural degeneration or dysfunction. Therapy may require not only therapeutic molecules, such as enzymes, but also widespread neural cell replacement.
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- Flax, J. D., Aurora, S., Yang, C., Simonin, C., Wills, A. M., Billinghurst, L. L., Jendoubi, M., Sidman, R. L., Wolfe, J. H., Kim, S. U., and Snyder, E. Y. (1998). Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat Biotechnol 16, 1033-1039.CrossRefPubMedGoogle Scholar
- Imitola, J., Comabella, M., Chandraker, A. K., Dangond, F., Sayegh, M. H., Snyder, E. Y., and Khoury, S. J. (2004a). Neural stem/progenitor cells express costimulatory mole-cules that are differentially regulated by inflammatory and apoptotic stimuli. Am J Pathol 164, 1615-1625.Google Scholar
- Imitola, J., Raddassi, K., Park, K. I., Mueller, F. J., Nieto, M., Teng, Y. D., Frenkel, D., Li, J., Sidman, R. L., Walsh, C. A., et al. (2004b). Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101, 18117-18122.CrossRefGoogle Scholar
- Jeyakumar, M., Thomas, R., Elliot-Smith, E., Smith, D. A., van der Spoel, A. C., d’Azzo, A., Perry, V. H., Butters, T. D., Dwek, R. A., and Platt, F. M. (2003). Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain 126, 974-987.CrossRefPubMedGoogle Scholar
- Shihabuddin, L. S., Numan, S., Huff, M. R., Dodge, J. C., Clarke, J., Macauley, S. L., Yang, W., Taksir, T. V., Parsons, G., Passini, M. A., et al. (2004). Intracerebral transplantation of adult mouse neural progenitor cells into the Niemann-Pick-A mouse leads to a marked decrease in lysosomal storage pathology. J Neurosci 24, 10642-10651.CrossRefPubMedGoogle Scholar
- Teng, Y. D., Lavik, E. B., Qu, X., Park, K. I., Ourednik, J., Zurakowski, D., Langer, R., and Snyder, E. Y. (2002). Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci USA 99, 3024-3029.CrossRefPubMedGoogle Scholar
- Vescovi, A. L., Gritti, A., Galli, R., and Parati, E. A. (1999). Isolation and intracerebral grafting of nontransformed multipotential embryonic human CNS stem cells. J Neuro-trauma 16, 689-693.Google Scholar
- Wenger, D. A., Rafi, M. A., Luzi, P., Datto, J., and Costantino-Ceccarini, E. (2000). Krabbe disease: Genetic aspects and progress toward therapy. Mol Genet M1-9.Google Scholar
- Yamanaka, S., Johnson, M. D., Grinberg, A., Westphal, H., Crawley, J. N., Taniike, M., Suzuki, K., and Proia, R. L. (1994). Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease. Proc Natl Acad Sci USA 91, 9975-9979.CrossRefPubMedGoogle Scholar
- Zlomanczuk, P., Mrugala, M., de la Iglesia, H. O., Ourednik, V., Quesenberry, P. J., Snyder, E. Y., and Schwartz, W. J. (2002). Transplanted clonal neural stem-like cells respond to remote photic stimulation following incorporation within the suprachias-matic nucleus. Exp Neurol 174, 162-168.CrossRefPubMedGoogle Scholar