Microencapsulation—A Novel Gene Therapy for Lysosomal Storage Diseases

  • Colin J. D. Ross
  • Patricia L. Chang


Over 30 different lysosomal storage diseases, each associated with deficiency of a specific lysosomal enzyme, have been described in man (Gieselmann 1995). Because of the ubiquitous presence of lysosomes in almost all cell types, deficiencies of these enzymes cause multisystem anomalies, often with catastrophic consequences, and frequently result in early death. Although the incidence of individual enzyme deficiency is rare, lysosomal storage diseases collectively occur in 1 in∼10,000 births. In spite of such significant prevalence and devastating consequences, there is no cure or even definitive treatment for most of these diseases. Until recently, bone marrow transplantation has been the only experimental treatment offered with some degree of success (Krivit et al 1990, Hoogerbrugge et al 1995). However, this procedure carries high rates of morbidity (graft-versus-host disease) and mortality (10% in matched and 20–25% in unmatched donors). Furthermore, even if the risks are acceptable, most patients (70%) cannot find compatible donors (Parkman 1986). In the majority of the affected families the only medical interventions available are palliative care until death occurs, and prevention of recurrence through prenatal diagnosis. An alternative treatment available to a subtype of one form of lysosomal storage disease is enzyme replacement. For the non-neuropathic form of Gaucher’s disease, administration of glucocerebrosidase, the deficient enzyme in question, has resulted in definite clinical imrovements. This therapy is now an accepted form of treatment in the U.S., but only for those who can afford it. Under the Orphan Drug Act, with no competitive markets, the annual cost for the enzyme Ceredase alone is $380,000/70 kg (FDA recommendation, 1991). Because of the risks and the dificulty in locating donors for bone marrow transplant, and the high cost for either bone marrow transplantation (>$ 100,000) or enzyme replacement treatment, more cost-effective therapies for the lysosomal storage diseases need to be developed. Since the genes for many lysosomal enzymes have been cloned, somatic gene therapy for lysosomal storage diseases may offer the ultimate solution to this serious healthcare problem (Beutler 1993).


Bone Marrow Transplantation Gauche Disease Lysosomal Storage Disease Bone Marrow Trans Metachromatic Leukodystrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aebischer P, Wahlberg L, Tresco PA, and Winn SR. 1991a. Macroencapsulation of dopamine-secreting cells by coextrusion with an organic polymer solution. Biomaterials. 12: 50–56.PubMedCrossRefGoogle Scholar
  2. Aebischer P, Tresco PA, Sagen J, and Winn SR. 1991b. Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats. Brain Res. 560: 43–49.PubMedCrossRefGoogle Scholar
  3. Al-Hendy A, Hortelano G, Tannenbaum GS, and Chang PL. 1995. Correction of the growth defect in dwarf mice with non-autologous micro-encapsulated myoblasts— an alternate approach to somatic gene therapy. Hum. GeneTher. 6: 165–175.Google Scholar
  4. Anderson WF. 1995. Gene therapy. Sci. Am. 273:124–128.PubMedGoogle Scholar
  5. Awrey D, Tse M, Hortelano G, and Chang PL. 1995. Permeability of alginate microcapsules to secretory recombinant gene products. Manuscript submittedGoogle Scholar
  6. Bastedo L, Sands MS, Hortelano B, Al-Hendy A, and Chang PL. 1994. Partial correction of murine mucopolysaccaridosis VII with micro-encapsulated non-autologous recombinant fibroblasts. Am. J. Hum. Genet. 55:A211.Google Scholar
  7. Bastedo L, Sands MS, Lambert DT, Pisa MA, Birkenmeier E, and Chang P. 1994. Behavioral consequences of bone marrow transplantation in the treatment of murine mucopolysaccharidosis type VII. J. Clin. Invest. 94:1180–1186.PubMedCrossRefGoogle Scholar
  8. Bergsma D, Desnick R, Bernlohr RW, and Krivit W. (eds) 1973. Enzyme therapy in genetic diseases. Baltimore: Williams & Wilkins for the National Foundation-March of Dimes, BD: OASIX (2).Google Scholar
  9. Bergstrom SK, Quinn JJ, Greenstein R, and Ascensao J. 1994. Long-term follow up of a patient transplanted for Hunter’s disease type IIB: a case report and literature review. Bone Marrow Trans. 14: 653–658.Google Scholar
  10. Beutler E. 1993. Gaucher disease as a paradigm of current issues regarding single gene mutations of humans. Proc. Natl. Acad. Sci. USA 90: 5384–5390.PubMedCrossRefGoogle Scholar
  11. Birkenmeier EH, Davisson MT, Beamer WG, Ganschow RE, Vogler CA, Gwynn B, Lyford KA, Maltais LM, and Wawrzyniak CJ. 1989. Murine mucopolysaccharidosis type VII-characterization of a mouse with μ-glucuronidase deficiency. J. Clin. Invest. 83: 1258–66.PubMedCrossRefGoogle Scholar
  12. Birkenmeier EH, Barker JE, Vogler CA, Kyle JW, Sly WS, Gwynn B, Levy B, and Pegors C. 1991. Increased life span and correction of metabolic defects in murine mucopolysaccharidosis type VII after syngeneic bone marrow transplantation. Blood. 78: 3081–3092.PubMedGoogle Scholar
  13. Breider MA, Shull RM, and Constantopoulos G. 1989. Long-term effects of bone marrow transplantation in dogs with mucopolysaccharidosis I. Am J Pathol. 134: 677–692.PubMedGoogle Scholar
  14. Brooks DA, McCourt PA, Gibson GJ, Ashton LJ, Shutter M, and Hopwood JJ. 1991. Analysis of N-acetylgalactosamine-4-sulfatase protein and kinetics in mucopolysaccharidosis type VI patients. Am. J. Hum. Genet. 48:710–719.PubMedGoogle Scholar
  15. Chang PL, Shen N, and Westcott AJ. 1993. Delivery of recombinant gene products with microencapsulated cells in vivo. Hum. Gene Ther. 4: 433–440.PubMedCrossRefGoogle Scholar
  16. Chang PL, Hortelano G, Tse M, and Awrey DE. 1994a. Growth of recombinant fibroblasts in alginate microcapsules. Biotech. Bioengin. 43: 925–933.CrossRefGoogle Scholar
  17. Chang PL, Lambert DT, and Pisa MA. 1994b. Behavioural abnormalities in a murine model of a human lysosomal storage disease. NeuroReport. 4: 507–510.CrossRefGoogle Scholar
  18. Chang PL. 1995. Non-autologous somatic gene therapy. In: Somatic gene therapy (Chang, PL, ed.) Boca Raton, Florida: CRC, Chap. 12.Google Scholar
  19. Clarke L, Russell CS, Pwnall S, Warrington CL, Borowski A, Dimmick JE, Toone J, and Jirik FR. 1997. Murine mucopolysaccharidosis type I: targeted disruption of the murine a-L-iduronidase gene. Hum. Mol. Gen. 6: 503–511.PubMedCrossRefGoogle Scholar
  20. Cohen-Tannoudji M et al. 1995. Disruption of murine Hexa gene leads to enzymatic deficiency and to neuronal lysosomal storage, similar to that observed in Tay-Sachs disease. Mam. Genome. 6: 844–849.CrossRefGoogle Scholar
  21. Correll PH, Fink JK, Brady RO, Perry LK, and Karlsson S. 1989. Production of human glucocerebrosidase in mice after retoroviral gene transfer into multipotential hematopoietic progenitor cells. Proc. Nat. Acad. Sci. USA. 86: 8912–8916.PubMedCrossRefGoogle Scholar
  22. Crawley AC, Brooks DA, Müller VJ, Petersen BA, Isaac EL, Bielicki J, King BM, Boulter CD, Moore AJ, Fazzalari NL, Anson DS, Byers S, and Hopwood JJ. 1996. Enzyme replacement therapy in a feline model of Maroteaux-Lamy syndrome. J. Clin. Invest. 97: 1864–1873.PubMedCrossRefGoogle Scholar
  23. Cunningham LA, Short MP, Vielkind U, Breakefield XO, and Bohn MC. 1991. Survival and differentiation within adult mouse striatum of grafted rat pheochromocytoma cells (PC 12) genetically modified to express recombinant β-NGF. Exp Neurobiol. 112: 174–182.CrossRefGoogle Scholar
  24. Desnick RJ, Dean KJ, Grabowski G, Bishop DF, and Sweeley CC. 1979. Enzyme therapy in Fabry disease-differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic alpha-galactosidase A isozymes. Proc. Natl. Acad. SCi. USA 76: 5326–5330.PubMedCrossRefGoogle Scholar
  25. Evers M, Saftig P, Schmidt P, Hafner A, McLogin DB, Schmahl W, Hess B, von Figura K, and Peters, C. 1996. Proc. Nat. Acad. Sci. USA. 93: 8214–8219.CrossRefGoogle Scholar
  26. Fink JK, Correll PH, Perry LK, Brady RO, and Karlsson S. 1990. Correction of glucocerebroside deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with disease. Proc. Nat. Acad. Sci. USA. 87: 2334–2338.PubMedCrossRefGoogle Scholar
  27. Food and Drug Administration 1991. FDA Med. Bull. 21:6–7.Google Scholar
  28. Gasper PW, Thrall MA, Wenger DA, Macy DW, Ham L, Dornsife RE, McBiles K, Quackenbush SL, Kesel ML, and Gillette EL. 1984. Correction of feline arylsulphatase B deficiency (mucopolysaccharidosis VI) by bone marrow transplantation. Nature. 312: 467–469.PubMedCrossRefGoogle Scholar
  29. Gieselmann V. 1995. Lysosomal storage disease. Biochim. Biophys. Acta Mol. Basis Dis. 1270: 103–136.CrossRefGoogle Scholar
  30. Ginns El, Choudary PV, Martin BM, Winnfield S, Stubblefield B, Mayor J, Merkle-Lehman D, Murray GJ, Bowers LA, and Barranger JA. 1984. Isolation of cDNA clones for human β-glucocerebrosidase using the Xgtl 1 expression system. Biochem. Biophys. Res. Comm. 123: 574–80.PubMedCrossRefGoogle Scholar
  31. Grabowski GA. 1993. Gaucher disease: Enzymology, genetics, and treatment. Adv. Hum. Genet. 21: 377–441.PubMedGoogle Scholar
  32. Hartley WJ, Canfield PJ, and Donnely TM. 1982. A suspected new canine storage disease. Acta Neuropathol. 56: 225–232.PubMedCrossRefGoogle Scholar
  33. Haskins ME, Jezyk PF, Desnick RJ, McDonaugh SK, and Patterson DF. 1979. Alpha-L-iduronidase deficiency in a cat: a model of mucopolysaccharidosis I. Pediat. Res. 13: 1294–1297.PubMedCrossRefGoogle Scholar
  34. Haskins ME, Aguirre GD, Jezyk PF, and Patterson DF. 1980. The pathology of the feline model of mucopolysaccharidosis VI. Am. J. Path. 101: 657–666.PubMedGoogle Scholar
  35. Haskins ME, Desnick RJ, DiFerrante N, Jezyk PF, and Patterson DF. 1984. μ-glucuronidase deficiency in a dog: a model of mucopolysaccharidosis type VII. Pediatr. Res 18: 980–984.PubMedGoogle Scholar
  36. Hatton JD, Lechtman AN, and U, HS. 1992. Formation of PC 12 tumors after implantation into rat brain: dependence of time course host stage. Cancer Res. 52: 1933–1937.PubMedGoogle Scholar
  37. Hoffman D, Breakefield XO, Short MP, and Aebischer P. 1993. Transplantation of a polymer-encapsulated cell line genetically engineered to release NGF. Exp. Neurol. 122: 100–106.PubMedCrossRefGoogle Scholar
  38. Hoogerbrugge PM, Brouwer OF, Bordigoni P, Ringden O, Kapaun P, Ortega JJ, O’Meara A, Cornu G, Souillet G, Frappaz. D, Blanche S, and Fischer A. 1995. Allogeneic bone marrow transplantation for lysosomal storage diseases. Lancet 345: 1398–1402.PubMedCrossRefGoogle Scholar
  39. Hortelano G, Al-Hendy-A and Chang PL. 1996. Delivery of factor IX in mice using implantable microcapsules: towards gene therapy of hemophilia B. Blood 87: 5095–5103.PubMedGoogle Scholar
  40. Jaeger CB. 1985. Immunocytochemical study of PC12 cells grafted into the brain of immature rats. Exp. Brain Res. 59: 615–624.PubMedCrossRefGoogle Scholar
  41. Jaeger CB, Kapoor R, and Llinas R. 1988. Cytology and organization of rat cerebellar organ cultures. Neuroscience. 26: 509–538.PubMedCrossRefGoogle Scholar
  42. Jezyk PF, Haskins ME, Patterson DF, Mellman WJ, and Greenstein M. 1977. Mucopolysaccharidosis in a cat with arylsulfatase B deficiency: a model of Maroteaux-Lamy syndrome. Science 198: 834–836.PubMedCrossRefGoogle Scholar
  43. Krivit W, Pierpont ME, Ayaz K, Tsai M, Ramsay NK Kersey JH, Weisdorf S, Sibley R, Snover D, and McGovern MM. 1984. Bone-marrow transplantation in the Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI). Biochemical and clinical status 24 months after transplantation. N. Engl. J. Med. 1984 311:1606–1611.PubMedCrossRefGoogle Scholar
  44. Krivit W, and Whitley CB. 1987. Bone marrow transplantation for genetic diseases. New Engl. J. Med. 316: 1085–7.PubMedCrossRefGoogle Scholar
  45. Krivit W, Whitley CB, Chang PN, Shapiro N, Belani KG, Snover D, Summers GC, and Blazar B. 1990. Lysosomal storage diseases treated by bone marrow transplantation: Review of 21 patients. In: Bone marrow transplantation in children (Johnson, FL and Pochedly, C, eds.) New York: Raven Press.Google Scholar
  46. Krivit W, Shapiro E, Hoogerbrugge PM, and Moser HW. 1992. State of the art review: bone marrow transplantation treatment for storage diseases. Bone Marrow Transplant. 10 Suppl. 1: 87–96.Google Scholar
  47. Kyle JW, Birkenmeier EH, Gwynn B, Vogler C, Hoppe PC, Hoffmann JW, and Sly WS. 1990. Correction of murine mucopolysaccharidosis VII by a human β-glucuronidase transgene. Proc. Natl. Acad. Sci. USA. 87: 3914–3918.PubMedCrossRefGoogle Scholar
  48. Lacorazza HD, Flax JD, Snyder EY, and Jendoubi M. 1996. Expression of human beta-hexosaminidase alphasubunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells. Nat. Med. 2: 424–429.PubMedCrossRefGoogle Scholar
  49. Ladisch S, Bayeuer E, Philipport M, and Feig S. 1986. Biochemical findings after bone marrow transplantation for metachromatic leukodystrophy: a preliminary report. Birth Defects. 22: 69–78.PubMedGoogle Scholar
  50. Lau C, Soriano HE, Ledley FD, Finegold MJ, Wolfe JH, Birkenmeier EH, and Henning SJ. 1995. Retro viral gene transfer into the intestinal epithelium. Hum. Gene Ther. 6: 1145–1155.PubMedCrossRefGoogle Scholar
  51. Li T, and Davidson BL. 1995. Phenotype correction in retinal pigment epithelium in murine mucopolysaccharidosis VII by adenovirus-mediated gene transfer. Proc. Natl. Acad. Sci. USA 92: 7700–7704.PubMedCrossRefGoogle Scholar
  52. Liu H, Ofosu FA, and Chang PL. 1993. Expression of human factor IX by microencapsulated recombinant fibroblasts. Hum. Gene Ther. 4: 291–301.PubMedCrossRefGoogle Scholar
  53. Liu Y, Hoffmann A, Grinberg A, Westphal H, McDonald MP, Miller KM, Crawley JN, Sandhoff K, Suzuki K, and Proia RL. 1997. Mouse model of GM2 activator deficiency manifests cerebellar pathology and motor impairment. Proc. Natl. Acad. Sci. USA. 94: 8138–8143.PubMedCrossRefGoogle Scholar
  54. Littlewood JD, Herrtage ME, and Palmer AC. 1983. Neuronal storage disease in English springer spaniels. Vet. Record. 112:86–87.CrossRefGoogle Scholar
  55. Marechal V, Naffakh N, Danos O, and Heard JM. 1993. Disappearance of lysosomal storage in spleen and liver of mucopolysaccharidosis VII mice after transplantation of genetically modified bone marrow cells. Blood. 82: 1358–65.PubMedGoogle Scholar
  56. McGovern MM, Mandell N, Haskins M, and Desnick RJ. 1985. Animal model studies of allelism: characterization of arylsulfatase B mutations in homoallelic and heteroallelic (genetic compound) homozygotes with feline mucopolysaccharidosis VI. Genetics. 110: 733–749.PubMedGoogle Scholar
  57. Miyazano M, Lee VM, and Trojanowski JQ. 1995. Proliferation, cell death, and neural differentiation in transplanted human embryonal carcinoma (Ntera2) cells depend on the graft site in nude and SCID mice. Lab. Invest. 73: 273–283.Google Scholar
  58. Moullier P, Bohl D, Heard J-M, and Danos O. 1993. Correction of lysosomal storage in the liver and spleen of MPS VII affected mice by implantation of genetically modified skin fibroblasts. Nat. Gen. 4: 154–159.CrossRefGoogle Scholar
  59. Myerowitz R and Proia RL. 1984. cDNA clone for the a-chain of human B-hexosaminidase: deficiency of a-chain mRNA in Ashkenazi Tay-Sachs fibroblasts. Proc. Natl. Acad. Sci. 81: 5394–8.PubMedCrossRefGoogle Scholar
  60. Naffakh N, Pinset C, Montarras D, Li Z, Paulin D, Danos O, and Heard J. 1996. Long term secretion of therapeutic proteins from genetically modified skeletal muscles. Hum. Gen. Ther. 7: 11–21.CrossRefGoogle Scholar
  61. Neufeld EF and Muenzer J. 1995. The mucopolysaccharidoses. In: The metabolic and molecular bases of inherited disease. (Scriver, CR, Beaudet, AL, Sly, WS, Valle, DV, eds. New York: McGraw-Hill Inc.Google Scholar
  62. Nimgaonkar, MT, Bahnson, AB, Mannion-Henderson, J, Barranger, JA, and Ball, ED. 1994. Hematopoietic stem cells as targets for gene therapy in Gaucher disease. Cold Spring Harbor Laboratory Meeting on Gene Therapy, p. 7, Sept, 1994.Google Scholar
  63. O’Dowd BF, Quan F, Willard HF, Lamhonwah AM, Korneluk RG, Lowden JA, Gravel RA, and Mahuran DJ. 1985. Isolation of cDNA clones coding for the beta subunit of human beta-hexosaminidase. Proc. Natl. Acad. Sci. USA. 82: 1184–8.PubMedCrossRefGoogle Scholar
  64. Ohashi T, Watabe K, Uehara K, Sly WS, Vogler C, and Eto Y. 1997. Adenovirus-mediated gene transfer and expression of human beta-glucuronidase gene in the liver, spleen, and central nervous system in mucopolysaccharidosis type VII mice. Proc. Natl. Acad. Sci. USA. 94: 1287–1292.PubMedCrossRefGoogle Scholar
  65. Oshima AJ, Kyle W, and Miller RD, Hoffmann JW, Powell PP, Grubb JH, Sly WS, Tropak M, Guise KS, and Gravel RA. 1987. Cloning, sequencing and expression of cDNA for human β-glucuronidase. Proc. Natl. Acad. Sci. 84: 685–9.PubMedCrossRefGoogle Scholar
  66. Otterback B and Stoffel W. 1995. Acid sphingomyelinasedeficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick disease). Cell. 81: 1053–1061.CrossRefGoogle Scholar
  67. Parkman R. 1986. The application of bone marrow transplantation to the treatment of genetic diseases. Science. 232: 1373–7.PubMedCrossRefGoogle Scholar
  68. Potter MA, Hymus SA, Stockley TL, and Chang PL. 1998. Suppression of immunological response against a transgene product delivered with microencapsulated cells. Hum. Gen. Ther. 9: 1275–1282.CrossRefGoogle Scholar
  69. Rappeport JM and Ginns El. 1984. Bone marrow transplantation in severe Gaucher’s disease. New Engl. J. Med. 311:84–8.PubMedCrossRefGoogle Scholar
  70. Ross CJD et al. 1998. Allogeneic gene therapy of the central nervous system in the murine model of mucopolysaccharidosis type VII: Treatment and behavioral recovery. Manuscript to be submitted.Google Scholar
  71. Salvetti A, Moullier P, Cornet V, Brooks D, Heard JM, and Danos O. 1994. Preclinical studies for the in vivo delivery of human a-iduronidase in mucopolysaccharidosis type I. Cold Spring Harbor Meeting on Gene Therapy, September, 1994 p. 146.Google Scholar
  72. Salvetti A, Moullier P, Cornet V, Brooks D, Hopwood JJ, Danos O, and Heard JM. 1995. In vivo delivery of human alpha-L-iduronidase in mice implanted with neo-organs. Hum. Gene Ther. 6: 1153–1159.PubMedCrossRefGoogle Scholar
  73. Sands MS, and Birkenmeier EH. 1993. A single-base-pair deletion in the beta-glucuronidase gene accounts for the phenotype of murine mucopolysaccharidosis type VII. Proc. Natl. Acad. Sci. U.S.A. 90: 6567–6571.PubMedCrossRefGoogle Scholar
  74. Sands MS, Vogler C, Kyle JW, Grubb JH, Levy B, Galvin N, Sly WS, and Birkenmeier EH. 1994. Enzyme replacement therapy for murine mucopolysaccharidosis type VIL J. Clin. Invest. 93: 2324–31.PubMedCrossRefGoogle Scholar
  75. Sands MS, Erway LC, Vogler C, Sly WS, and Birkenmeier EH. 1995. Syngeneic bone marrow transplantation reduces the hearing loss associated with murine mucopolysaccharidosis type VII. Blood. 86: 2033–2040.PubMedGoogle Scholar
  76. Schinstine M, Fiore DM, Winn SR, and Emerich DF. 1995. Polymer-encapsulated schwannoma cells expressing human nerve growth factor promote the survival of cholinergic neurons after a fimbria-fornix transfection. Cell Transplant. 4: 93–102.PubMedCrossRefGoogle Scholar
  77. Shull RM, Munger RJ, Spellacy E, Hall CW, Constantopoulos G, and Neufeld EF. 1982. Canine alpha-Liduronidase deficiency: a model of mucopolysaccharidosis I. Am. J. Path. 109: 244–248.PubMedGoogle Scholar
  78. Shull RM, Xiaochen L, McEntree MF, Bright RM, Pepper KA, and Kohn DB. 1996. Myoblast gene therapy in canine MPS I: Abrogation by an immune response to a-L-iduronidase. Hum. Gene Ther. 7: 1596–1603.CrossRefGoogle Scholar
  79. Shull RM, Kakkis ED, McEntree MF, Kania SA, Jonas AJ, and Neufeld EF. 1994. Enzyme replacement in a canine model of Hurler syndrome. Proc. Nat. Acad. Sci. USA. 91: 12937–12941.PubMedCrossRefGoogle Scholar
  80. Simonaro CM, Haskins ME, Kunieda T, Evans SM, Visser JW, and Schuchman EH. 1997. Bone marrow transplantation in newborn rats with mucopolysaccharidosis type VI: biochemical, pathological, and clinical findings. Transplantation. 63: 1386–1393.PubMedCrossRefGoogle Scholar
  81. Sly WS, Quinton BA, McAlister WH, and Rimoin DL. 1973. ß-glucuronidase deficiency: report of clinical, radiologie, and biochemical features of a new mucopolysaccharidosis. J. Pediatr. 82: 249–257.PubMedCrossRefGoogle Scholar
  82. Sly WS, and Vogler C. 1997. Gene therapy for lysosomal storage disease: a no-brainer? Transplants of fibroblasts secreting high levels of beta-glucuronidase decrease lesions in the brains of mice with Sly syndrome, a lysosomal storage disease. Nat. Med. 3: 719–720.PubMedCrossRefGoogle Scholar
  83. Snyder EY, Taylor RM, and Wolfe JH. 1995. Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. Nature. 374: 367–70.PubMedCrossRefGoogle Scholar
  84. Sorge J, West C, Westwood B, and Beutler E. 1985. Molecular cloning and nucleotide sequence of human glucocerebrosidase cDNA. Proc. Natl. Acad. Sci. 82: 7289–93.PubMedCrossRefGoogle Scholar
  85. Spellacy E, Shull RM, Constantopoulos G, and Neufeld EF. 1983. A canine model of human alpha-L-iduronidase deficiency. Proc. Nat. Acad. Sci. 80: 6091–6095.PubMedCrossRefGoogle Scholar
  86. Stein C, Gieselmann V, Kreysing J, Schmidt B, Pohlman R, Waheed A, and von Figura K. 1989. Cloning and expression of human arylsulfatase A. J. Biol. Chem. 264: 1252–9.PubMedGoogle Scholar
  87. Taylor RM, Stewart GJ, and Farrow BRH. 1989. Improvement in the neurological signs and storage lesions of fucosidoses in dogs given marrow transplants at an early age. Transplant. Proc. 21: 3818–9.PubMedGoogle Scholar
  88. Taylor RM, and Wolfe, JH. 1994. Cross-correction of ß-glucuronidase deficiency by retroviral vector-mediated gene transfer. Exp. Cell Res. 214: 606–613.PubMedCrossRefGoogle Scholar
  89. Taylor RM, and Wolfe JH. 1997. Decreased lysosomal storage in the adult MPS VII mouse brain in the vicinity of grafts of retroviral vector-corrected fibroblasts secreting high levels of beta-glucuronidase. Nat. Med. 3: 771–774.PubMedCrossRefGoogle Scholar
  90. Thomas GH. 1994. “Pseudodeficiencies” of lysosomal hydrolases. Am. J. Hum. Genet. 54: 934–940.PubMedGoogle Scholar
  91. Thompson JN, Jones MZ, Dawson G, and Huffman PS. 1992. N-acetylglucosamine 6-sulphatase deficiency in a Nubian goat: a model of Sanfilippo syndrome type D (mucopolysaccharidosis HID). J. Inherit. Metab. Dis. 15: 760–768.PubMedCrossRefGoogle Scholar
  92. Tresco PA, Winn SR, Tan S, Jaeger CB, Greene LA, and Aebischer P. 1992. Polymer encapsulated PC-12 cells: Long term survival and associated reduction in lesion induced rotational behavior. Cell Transplant. 1: 255–264.PubMedGoogle Scholar
  93. Vandevelde M, Fankhauser R, Bichsel P, Wiesmann U, and Herschkowitz N. 1982. Hereditary neurovisceral mannosidosis associated with alpha-mannosidase deficiency in a family of Persian cats. Acta Neuropathol.(Berl.) 58: 64–68.CrossRefGoogle Scholar
  94. Vellodi A, Hobbs JR, O’Donnel NM, Coulter BS, and Hugh-Jones K. 1987. Treatment of Neiman-Pick disease type B by allogeneic bone marrow transplantation. Brit. Med. J. 295: 1375–1376.CrossRefGoogle Scholar
  95. Vellodi A, Young E, New M, Pot-Mees C, and Hugh-Jones K. 1992. Bone marrow transplantation for Sanfilippo disease type B. J. Inherit. Metab. Dis. 15: 911–918.PubMedCrossRefGoogle Scholar
  96. Vogler C, Birkenmeier EH, Sly WS, Levy B, Pegors C, Kyle JW, and Beamer WG. 1990. A murine model of mucopolysaccharidosis VII-gross and microscopic findings in beta-glucuronidase-deficient mice. Am. J. Pathol. 136:207–17.PubMedGoogle Scholar
  97. Vogler C, Sands M, Higgins A, Levy B, Grubb J, Birkenmeier EH, and Sly WS. 1993. Enzyme replacement with recombinant beta-glucuronidase in the newborn mucopolysaccharidosis type VII mouse. Pediatr. Res. 34: 837–840.PubMedCrossRefGoogle Scholar
  98. Walkley SU, Thrall MA, Dobrenis K, Huang M, March PA, Siegel DA, and Wurzelmann S. 1994. BMT corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease. Proc. Nat. Acad. Sci. USA. 91: 2970–2974.PubMedCrossRefGoogle Scholar
  99. Wilson JM. 1996. Animal models of human disease for gene therapy. J. Clin. Invest. 97: 1138–1141.PubMedCrossRefGoogle Scholar
  100. Winn SR, Tresco PA, Zielinski B, Greene LA, Jaeger CB, and Aebischer P. (1991) Behavioral recovery following intrastriatal implantation of microencapsulated PC 12 cells. Exp. Neurobiol. 113: 322–329.CrossRefGoogle Scholar
  101. Wolfe, JH, Deshmane SL, and Fraser, NW. (1992a) Herpes virus vector gene transfer and expression of betaglucuronidase in the central nervous system of MPS VII mice. Nat. Genet. 1: 379–84.PubMedCrossRefGoogle Scholar
  102. Wolfe JH, Sands MS, Barker JE, Gwynn B, Rowe LB, Vogler CA, and Birkenmeier EH. (1992b) Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer. Nature. 360: 749–753.PubMedCrossRefGoogle Scholar
  103. Yamanaka S, Johnson MD, Grinberg A, Westphal H, Crawley JN, Taniike M, Suzuki K, and Proia RL. (1994) Targeted disruption of the hexa gene results in mice with biochemical and pathological features of Tay-Sachs disease. Proc. Nat. Acad. Sci. USA. 91: 9975–9979.PubMedCrossRefGoogle Scholar
  104. Yoshida M, Ikadai H, Maekawa A, Takahashi M, and Nagase S. (1993) Pathological characteristics of mucopolysaccharidosis VI in the rat. J. Comp. Pathol. 109: 141–153.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Colin J. D. Ross
  • Patricia L. Chang

There are no affiliations available

Personalised recommendations