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Gene Therapy for Neurological Disorders and Brain Tumors pp 409–418Cite as

Gene Therapy for Lysosomal Storage Diseases

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Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

The lysosomal storage diseases (LSDs) present a unique opportunity and challenge for the field of gene therapy. LSDs are caused by a deficiency in any one of over 40 individual lysosomal enzymes necessary for the breakdown and reutilization of important lipids, carbohydrates, and proteins. Individually, the diseases occur infrequently, but collectively the incidence has been estimated at 1/5000 births (1). The LSDs have been well characterized regarding the neuropathology, enzymology, clinical course, and, most recently, the partial molecular understanding of the enzymes and activators (2). This information allows for the strategic planning of potential genetic therapies for these diseases. The challenge in these disorders is to devise a therapy that will not only alleviate the enzyme deficiency in systemic organs, but concomitantly correct the defect within the central nervous system (CNS).

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References

  1. Kornfeld, S. and Sly, W. S. (1985) Lysosomal storage defects. Hosp. Pract. 20, 78–82.

    Google Scholar 

  2. Moser, H. W. (1996) Neurodystrophies and neurolipidoses, in Handbook of Clinical Neurology, vol. 66 ( Vinken, P. J. and Bruyn, G. W., eds.). Elsevier, Amsterdam, pp. 123–387.

    Google Scholar 

  3. Nixon, R. A. and Cataldo, A. M. (1995) The endosomal-lysosomal system of neurons: new roles. Trends Neurosci. 18, 489–496.

    Article  PubMed  CAS  Google Scholar 

  4. von Figura, K. and Hasilik, A. (1986) Lysosomal enzymes and their receptors. Annu. Rev. Biochem. 55, 167–193.

    Article  PubMed  CAS  Google Scholar 

  5. Neufeld, E. F. (1991) Lysosomal storage diseases. Annu. Rev. Biochem. 60, 257–280.

    Article  PubMed  CAS  Google Scholar 

  6. Ioannou, Y. A., Bishop, D. F., and Desnick, R. F. (1992) Overexpression of human alphagalactosidase. A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion. J. Cell Biol. 119, 1137–1150.

    Article  PubMed  CAS  Google Scholar 

  7. Pfeffer, S. R. (1991) Targeting of proteins to the lysosome. Curr. Top. Microbiol. Immunol. 170, 43–65.

    Article  PubMed  CAS  Google Scholar 

  8. Leinekugel, P., Michel, S., Conzelmann, E., and Sandhoff, K. (1992) Quantitative correlation between the residual activity of beta-hexosaminidase A and arylsulfatase A and the severity of the resulting lysosomal storage disease. Hum. Genet. 88, 513–523.

    Article  PubMed  CAS  Google Scholar 

  9. Gieselmann, V. (1991) An assay for the rapid detection of the arylsulfatase A pseudodeficiency allele facilitates diagnosis and genetic counseling for metachromatic leukodystrophy. Hum. Genet. 86, 251–255.

    Article  PubMed  CAS  Google Scholar 

  10. Danes, B. S. and Bearn, A. G. (1966) Hurler’s syndrome: a genetic study in cell culture. J. Exp. Med. 123, 1–16.

    Article  PubMed  CAS  Google Scholar 

  11. Neufeld, E. F. and Fratantoni, J. C. (1970) Inborn errors of mucopolysaccharide metabolism. Science 169, 141–146.

    Article  PubMed  CAS  Google Scholar 

  12. Enomaa, N., Danos, O., Peltonen, L., and Jalanko, A. (1995) Correction of deficient enzyme activity in a lysosomal storage disease, aspartylglucosaminuria, by enzyme replacement and retroviral gene transfer. Hum. Gene Ther. 6, 723–731.

    Article  PubMed  CAS  Google Scholar 

  13. Xu, Y. H., Wenstrup, R., and Grabowski, G. A. (1995) Effect of cellular type on expression of acid (3-glucosidase: implications for gene therapy in Gaucher disease. Gene Ther. 2, 647–654.

    PubMed  CAS  Google Scholar 

  14. Gama Sosa, M. A., De Gasperi, R., Undevia, S., et al. (1996) Correction of the galactocerebrosidase deficiency in globoid cell leukodystrophy-cultured cells by SL3–3 retroviralmediated gene transfer. Biochem. Biophys. Res. Commun. 218, 766–771.

    Article  PubMed  CAS  Google Scholar 

  15. Ohashi, T., Matalon, R., Barranger, J. A., and Eto, Y. (1995) Overexpression of arylsulfatase A gene in fibroblasts from metachromatic leukodystrophy patients does not induce a new phenotype. Gene Ther. 2, 363–368.

    PubMed  CAS  Google Scholar 

  16. Anson, D. S., Muller, V., Bielicki, J., Harper, G. S., and Hopwood, J. J. (1993) Overexpression of N-acetylgalactosamine-4-sulfatase induces a multiple sulfatase deficiency in mucopolysaccharidosis-type VI fibroblasts. Biochem. J. 294, 657–662.

    PubMed  CAS  Google Scholar 

  17. Learish, R., Ohashi, T., Robbins, P. A., et al. (1996) Retroviral gene transfer and sustained expression of human arylsulfatase A. Gene Ther. 3, 343–349.

    PubMed  CAS  Google Scholar 

  18. Ohashi, T., Boggs, S., Robbins, P., et al. (1992) Efficient transfer and sustained high expression of the human glucocerebrosidase gene in mice and their functional macrophages following transplantation of bone marrow transduced by a retroviral vector. Proc. Natl. Acad. Sci. USA 89, 11,332–11, 336.

    Google Scholar 

  19. Barton, N. W., Brady, R. O., Dambrosia, J. M., et al. (1991) Replacement therapy for inherited enzyme deficiency-macrophage-targeted glucocerebrosidase for Gaucher’s disease. N. Engl. J. Med. 324, 1464–1470.

    Article  PubMed  CAS  Google Scholar 

  20. Grabowski, G. A., Bove, K., Daugherty, C., and Prows, C. (1994) Clinical and pathologic outcome of enzyme therapy in the severe neuronopathic variant Gaucher disease: implications in long-term therapy in non-neuronopathic variants. Am. J. Hum. Genet. 55S: A7.

    Google Scholar 

  21. Sands, M. S., Vogler, C., Kyle, J. W., et al. (1994) Enzyme replacement therapy for murine mucopolysaccharidosis type VII. J. Clin. Invest. 93, 2324–2331.

    Article  PubMed  CAS  Google Scholar 

  22. Krivit, W., Sung, J. H., Shapiro, E. G., and Lockman, L. A. (1995) Microglia: the effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal and peroxisomal storage diseases. Cell Transplantation 4, 385–392.

    Article  PubMed  CAS  Google Scholar 

  23. Krivit, W., Shapiro, E., Hoogerbrugge, P. M., and Moser, H. W. (1992) State of the art review: bone marrow transplantation treatment for storage disease. Bone Marrow Transplantation 10, 87–97.

    PubMed  Google Scholar 

  24. Tsai, P., Lipton, J. M., Sandev, I., et al. (1992) Allogenic bone marrow transplantation in severe Gaucher disease. Pediatr. Res. 31, 503–507.

    Article  PubMed  CAS  Google Scholar 

  25. Hoogerbrugge, P. M., Brouwer, O. F., Bordigoni, P., et al. (1995) Allogeneic bone marrow transplantation for lysosomal storage diseases. The European Group for Bone Marrow Transplantation. Lancet 345, 1398–1402.

    Article  PubMed  CAS  Google Scholar 

  26. Krivit, W., Shapiro, E. G., Lockman, L. A., et al. (1996) Bone marrow transplantation treatment for globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy, and Hurler syndrome, in Neurodystrophies and Neurolipidoses, vol. 66. ( Moser, H. W., ed.). Elsevier, Amsterdam, pp. 87–106.

    Google Scholar 

  27. Shapiro, E. G., Lockman, L. A., Balthazor, M., and Krivit, W. (1995) Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation. J. Inherited Metab. Dis. 18, 413–429.

    Article  PubMed  CAS  Google Scholar 

  28. Hoogerbrugge, P. M., Suzuki, K., Suzuki, K., et al. (1988) Donor-derived cells in the central nervous system of twitcher mouse after bone marrow transplantation. Science 239, 1035–1038.

    Article  PubMed  CAS  Google Scholar 

  29. Sands, M. S., Barker, J. E., Vogler, C., et al. (1993) Treatment of murine mucopolysaccharidosis type VII by syngeneic bone marrow transplantation in neonates. Lab. Invest. 68, 676–686.

    PubMed  CAS  Google Scholar 

  30. Bastedo, L., Sands, M. S., Lambert, D. T., Pisa, M. A., Birkenmeier, E., and Chang, P. L. (1994) Behavioral consequences of bone marrow transplantation in the treatment of murine mucopolysaccharidosis type VII. J. Clin. Invest. 94, 1180–1186.

    Article  PubMed  CAS  Google Scholar 

  31. Shull, R. M., Breider, M. A., and Constantopoulos, G. C. (1988) Long-term neurological effects of bone marrow transplantation in a canine lysosomal storage disease. Pediatr. Res. 24, 347–352.

    Article  PubMed  CAS  Google Scholar 

  32. Taylor, R. M., Farrow, B. R. H., and Stewart, G. J. (1992) Amelioration of clinical disease following bone marrow transplantation in fucosidase-deficient dogs. Am. J. Med. Genet. 42, 628–632.

    Article  PubMed  CAS  Google Scholar 

  33. Walkley, S. U., Thrall, M. A., Dobrenis, K., et al. (1994) Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease. Proc. Natl. Acad. Sci. USA 91, 2970–2974.

    Article  PubMed  CAS  Google Scholar 

  34. Yaeger, A. M., Shinn, C., Hart, C., and Pardoll, D. M. (1992) Repopulation by donor-derived macrophages in the murine central nervous system (CNS) after congenic bone marrow transplantation: a quantitative study. Blood 80, 269A.

    Google Scholar 

  35. Krall, W. J., Challita, P. M., Perlmutter, L. S., Skelton, D. C., and Kohn, D. B. (1994) Cells expressing human glucocerebrosidase from a retroviral vector repopulate macrophages and central nervous system microglia after murine bone marrow transplantation. Blood 83, 2737–2748.

    PubMed  CAS  Google Scholar 

  36. Unger, E. R., Sung, J. H., Manivel, J. C., Cheggis, M. L., Blazar, B. R., and Krivit, W. (1993) Male donor-derived cells in the brains of female sex-mismatched bone marrow transplant recipients: a Y-chromosome specific in-situ hybridization study. J. Neuropathol. Exp. Neurol. 52, 460–470.

    Article  PubMed  CAS  Google Scholar 

  37. Yazaki, M., Ohno, T., Matsubayashi, T., et al. (1995) Detection of donor lymphocytes in the cerebrospinal fluid of a patient with metachromatic leukodystrophy following bone marrow transplantation. Bone Marrow Transplantation 15, 137–139.

    PubMed  CAS  Google Scholar 

  38. Fink, J. K., Correll, P. H., Perry, L. K., Brady, R. O., and Karlsson, S. (1990) Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease. Proc. Natl. Acad. Sci. USA 87, 2334–2338.

    Article  PubMed  CAS  Google Scholar 

  39. Nolta, J. A., Yu, X. J., Bahner, I., and Kohn, D. B. (1992) Retroviral-mediated transfer of the human glucocerebrosidase gene into cultured Gaucher bone marrow. J. Clin. Invest. 90, 342–348; Erratum. J. Clin. Invest. 90, p. 1634.

    Article  Google Scholar 

  40. Wolfe, J. H., Sands, M. S., Barker, J. E., et al. (1992) Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer. Nature 360, 749–753.

    Article  PubMed  CAS  Google Scholar 

  41. Marechal, V., Naffakh, N., Danos, O., and Heard, J. M. (1993) Disappearance of lysosomal storage in spleen and liver of mucopolysaccharidosis VII mice after transplantation of genetically modified bone marrow cells. Blood 82, 1358–1365.

    PubMed  CAS  Google Scholar 

  42. Kantoff, P. W., Flake, A. W., Eglitis, M. A., et al. (1989) In utero gene transfer and expression: a sheep transplantation model. Blood 73, 1066–1073.

    PubMed  CAS  Google Scholar 

  43. Moullier, P., Marechal, V., Danos, O., and Heard, J. M. (1993) Continuous systemic secretion of lysosomal enzyme by genetically modified mouse skin fibroblasts. Transplantation 56, 427–432.

    Article  PubMed  CAS  Google Scholar 

  44. Moullier, P., Bohl, D., Heard, J. M., and Danos, O. (1993) Correction of lysosomal storage in the liver and spleen of MPS VII mice by implantation of genetically modified skin fibroblasts. Nature Genet. 4, 154–159.

    Article  PubMed  CAS  Google Scholar 

  45. Moullier, P., Bohl, D., Cardosa, J., Heard, J. M., and Danos, O. (1995) Long-term delivery of a lysosomal enzyme by genetically modified fibroblasts in dogs. Nature Med. 1, 353–357.

    Article  PubMed  CAS  Google Scholar 

  46. Naffakh, N., Pinset, C., Montarras, D., Pastoret, C., Danos, O., and Heard, J. M. (1993) Transplantation of adult-derived myoblasts in mice following gene transfer. Neuromuscular Disord. 3, 413–417.

    Article  CAS  Google Scholar 

  47. Breakefield, X. 0., Sena-Esteves, M., Pechan, P., et al. (1996) Gene therapy for the nervous system—status 1996. Genetic Therapy Fundacion, BBV.

    Google Scholar 

  48. Wolfe, J. H., Deshmane, S. L., and Fraser, N. W. (1992) Herpesvirus vector gene transfer and expression of ß-glucuronidase in the central nervous system of MPS VII mice. Nature Genet. 1, 379–384.

    Article  PubMed  CAS  Google Scholar 

  49. Davidson, B. L., Allen, E. D., Kozarsky, K. F., Wilson, J. M., and Roessler, B. J. (1993) A model system for in vivo gene transfer into the central nervous system using an adenoviral vector. Nature Genet. 3, 219–223.

    Article  PubMed  CAS  Google Scholar 

  50. Akli, S., Caillaud, C., Vigne, E., et al. (1993) Transfer of a foreign gene into the brain using adenovirus vectors. Nature Genet. 3, 224–228.

    Article  PubMed  CAS  Google Scholar 

  51. Li, T. and Davidson, B. L. (1995) Phenotype correction in retinal pigment epithelium in murine mucopolysaccharidosis VII by adenovirus-mediated gene transfer. Proc. Natl. Acad. Sci. USA 92, 7700–7704.

    Article  PubMed  CAS  Google Scholar 

  52. Doran, S. E., Xiao, D. R., Betz, A. L., et al. (1995) Gene expression from recombinant viral vectors in the central nervous sytem after blood—brain barrier disruption. Neurosurgery 36, 965–970.

    Article  PubMed  CAS  Google Scholar 

  53. Sabate, O., Horellou, P., Vigne, E., et al. (1995) Transplantation to the rat brain of human neural progenitors that were genetically modified using adenoviruses. Nature Genet. 9, 256–260.

    Article  PubMed  CAS  Google Scholar 

  54. Snyder, E. Y., Taylor, R. M., and Wolfe, J. H. (1995) Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. Nature 374, 367–370.

    Article  PubMed  CAS  Google Scholar 

  55. Lacorazza, H. D., Flax, J. D., Snyder, E. Y., and Jendoubi, M. (1996) Expression of human (3-hexosaminidase a-subunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells. Nature Med. 2, 424–429.

    Article  PubMed  CAS  Google Scholar 

  56. Aebischer, P., Tresco, P. A., Winn, S. R., Greene, L. A., and Jaeger, C. B. (1991) Long-term cross-species brain transplantation of a polymer-encapsulated dopamine-secreting cell line. Exp. Neurol. 111, 269–275.

    Article  PubMed  CAS  Google Scholar 

  57. Anderson, W. F. (1994) Gene therapy for genetic diseases. Hum. Gene Ther. 5, 281–282.

    Article  PubMed  CAS  Google Scholar 

  58. Berenson, R. J. (1992) Transplantation of CD34+ hematopoietic precursors: clinical rationale. Transplantation Proc. 24, 3032–3034.

    CAS  Google Scholar 

  59. Bregni, M., Magni, M., Siena, S., DiNicola, M., Bonadonna, G., and Gianni, A. M. (1992) Human peripheral blood hematopoietic progenitors are optimal targets of retroviral-mediated gene transfer. Blood 80, 1418–1422.

    PubMed  CAS  Google Scholar 

  60. Bahnson, A. B., Nimgaonkar, M., Fei, Y., et al. (1994) Transduction of CD34+ enriched cord blood and Gaucher bone marrow cells by a retroviral vector carrying the glucocerebrosidase gene. Gene Ther. 1, 176–184.

    PubMed  CAS  Google Scholar 

  61. Pereira, R. F., Halford, K. W., O’Hara, M. D., et al. (1995) Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc. Natl. Acad. Sci. USA 92, 4857–4861.

    Article  PubMed  CAS  Google Scholar 

  62. Platt, F. M. and Butters, T. D. (1995) Inhibitors of glycosphingolipid biosynthesis. Trends Glycosci. Glycotechnol. 7, 495–511.

    Article  CAS  Google Scholar 

  63. Kaye, E. M., Alroy, J., Raghavan, S. S., et al. (1992) Dysmyelinogenesis in animal model of GM1 gangliosidosis. Pediatr. Neurol. 8, 255–261.

    Article  PubMed  CAS  Google Scholar 

  64. Tsukamoto, M., Ochiya, T., Yoshida, S., Sugimura, T., and Terada, M. (1995) Gene transfer and expression in progeny after intravenous DNA injection into pregnant mice. Nature Genet. 9, 243–248.

    Article  PubMed  CAS  Google Scholar 

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  1. Edward M. Kaye
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Editors and Affiliations

  1. Molecular Neuro-Oncology, Neurosurgical Service, Massachussetts General Hospital, Harvard Medical School, Boston, MA, USA

    E. Antonio Chiocca MD, PhD

  2. Neurogenetics Unit, Massachussetts General Hospital, Harvard Medical Center, Boston, MA, USA

    Xandra O. Breakefield PhD

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Kaye, E.M. (1998). Gene Therapy for Lysosomal Storage Diseases. In: Chiocca, E.A., Breakefield, X.O. (eds) Gene Therapy for Neurological Disorders and Brain Tumors. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-478-8_19

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  • DOI: https://doi.org/10.1007/978-1-59259-478-8_19

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5314-1

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