Skip to main content
SpringerLink
Log in
Book cover

Gene Therapy of Autoimmune Diseases pp 1–16Cite as

Gene Therapy Approaches for Autoimmune Diseases of the Central Nervous System and Other Tissues

  • Chapter

  • 455 Accesses

Part of the book series: Medical Intelligence Unit ((MIUN))

Conclusions

The gene therapy of autoimmunity has held many promises for the last ten years, owing to its potential as an alternative therapeutic approach for diseases lacking a definitive cure and with a devastating social impact. However, there are still several issues to solve before these approaches would be transferable to humans.

Some studies are conceptually non applicable to human diseases. For instance, T and B cell-based antigen-specific approaches are difficult to translate into the clinical practice since the pathogenic (auto)antigens in MS, RA, and IDDM are not yet completely identified and antigen heterogeneity occurs in patients during the course of the disease. From a technological point of view, many gene transfer tools cannot be used in humans due to their (i) toxicity or immunogenicity (i.e., Vaccinia virus, HSV-1, first generation adenoviral vectors), (ii) scarce gene transfer efficiency (i.e., naked DNA, liposomes), and (iii) short-term expression (Vaccinia, HSV-1, naked DNA, liposomes).

However, the huge amounts of data generated in the last decade in experimental models have been very instrumental to weight the potential detrimental vs. protective effect of this novel therapeutic approach. We know for example that it is much more safer and efficacious to transfer the “therapeutic” gene directly into the autoimmune target organ rather than into the systemic circulation. This approach has several advantages: (i) restricted area (i.e., the CSF and the synovia) to target thus more efficient gene transfer, (ii) higher levels of transgene expression in the damaged/target area; and, (iii) no peripheral side/toxic effects.

In conclusion, while gene therapy approaches of autoimmune diseases are promising, there is a long way ahead before envisaging a wide application of this new technology in human diseases. While gene therapy approaches aimed to recovery loss of functions have shown in experimental models of autoimmunity great efficacy and reproducibility, without over toxic effect, there is still a lot to do for gene therapy protocols aimed to replace non-functioning organs.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Evans CH, Robbins PD, Ghivizzani SC et al. Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 1996; 7:1261–1280.

    PubMed  CAS  Google Scholar 

  2. Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med 2001; 7:33–40.

    Article  PubMed  CAS  Google Scholar 

  3. Martino G, Poliani PL, Marconi PC et al. Cytokine gene therapy of autoimmune demyelination revisited using herpes simplex virus type-1-derived vectors. Gene Ther 2000; 7:1087–1093.

    Article  PubMed  CAS  Google Scholar 

  4. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature 1996; 383:787–793.

    Article  PubMed  CAS  Google Scholar 

  5. Adorini L. Cytokine-based immunointervention in the treatment of autoimmune diseases. Clin Exp Immunol 2003; 132:185–192.

    Article  PubMed  CAS  Google Scholar 

  6. Croxford JL, Triantaphyllopoulos K, Podhajcer OL et al. Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system. J Immunol 1998; 160:5181–5187.

    PubMed  CAS  Google Scholar 

  7. Triantaphyllopoulos KA, Williams RO, Tailor H et al. Amelioration of collagen-induced arthritis and suppression of interferon-gamma, interleukin-12, and tumor necrosis factor alpha production by interferon-beta gene therapy. Arthritis Rheum 1999; 42:90–99.

    Article  PubMed  CAS  Google Scholar 

  8. Willenborg DO, Fordham SA, Cowden WB et al. Cytokines and murine autoimmune encephalomyelitis: inhibition or enhancement of disease with antibodies to select cytokines, or by delivery of exogenous cytokines using a recombinant vaccinia virus system. Scand J Immunol 1995; 41:31–40.

    Article  PubMed  CAS  Google Scholar 

  9. Furlan R, Brambilla E, Ruffini F et al. Intrathecal delivery of IFN-gamma protects C57BL/6 mice from chronic-progressive experimental autoimmune encephalomyelitis by increasing apoptosis of central nervous system-infiltrating lymphocytes. J Immunol 2001; 167:1821–1829.

    PubMed  CAS  Google Scholar 

  10. Otani K, Nita I, Macaulay W et al. Suppression of antigen-induced arthritis in rabbits by ex vivo gene therapy. J Immunol 1996; 156:3558–3562.

    PubMed  CAS  Google Scholar 

  11. Oligino T, Ghivizzani S, Wolfe D et al. Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis. Gene Ther 1999; 6:1713–1720.

    Article  PubMed  CAS  Google Scholar 

  12. Hung GL, Galea-Lauri J, Mueller GM et al. Suppression of intra-articular responses to interleukin-1 by transfer of the interleukin-1 receptor antagonist gene to synovium. Gene Ther 1994; 1:64–69.

    PubMed  CAS  Google Scholar 

  13. Makarov SS, Olsen JC, Johnston WN et al. Suppression of experimental arthritis by gene transfer of interleukin 1 receptor antagonist cDNA. Proc Natl Acad Sci USA 1996; 93:402–406.

    Article  PubMed  CAS  Google Scholar 

  14. Bandara G, Mueller GM, Galea-Lauri J et al. Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer. Proc Natl Acad Sci USA 1993; 90:10764–10768.

    Article  PubMed  CAS  Google Scholar 

  15. Bakker AC, Joosten LA, Arntz OJ et al. Prevention of murine collagen-induced arthritis in the knee and ipsilateral paw by local expression of human interleukin-1 receptor antagonist protein in the knee. Arthritis Rheum 1997; 40:893–900.

    Article  PubMed  CAS  Google Scholar 

  16. Roessler BJ, Hartman JW, Vallance DK et al. Inhibition of interleukin-1-induced effects in synoviocytes transduced with the human IL-1 receptor antagonist cDNA using an adenoviral vector. Hum Gene Ther 1995; 6:307–316.

    PubMed  CAS  Google Scholar 

  17. Martino G, Poliani PL, Marconi PC et al. Cytokine gene therapy of autoimmune demyelination revisited using herpes simplex virus type-1-derived vectors. Gene Ther 2000; 7:1087–1093.

    Article  PubMed  CAS  Google Scholar 

  18. Shaw MK, Lorens JB, Dhawan A et al. Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis. J Exp Med 1997; 185:1711–1714.

    Article  PubMed  CAS  Google Scholar 

  19. Piccirillo CA, Prud’homme GJ. Prevention of experimental allergic encephalomyelitis by intramuscular gene transfer with cytokine-encoding plasmid vectors. Hum Gene Ther 1999; 10:1915–1922.

    Article  PubMed  CAS  Google Scholar 

  20. Garren H, Ruiz PJ, Watkins TA et al. Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway. Immunity 2001; 15:15–22.

    Article  PubMed  CAS  Google Scholar 

  21. Broberg E, Setala N, Roytta M et al. Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis Gene Ther 2001; 8:769–777.

    Article  PubMed  CAS  Google Scholar 

  22. Furlan R, Poliani PL, Galbiati F et al. Central nervous system delivery of interleukin-4 by a non-replicative herpes simplex type 1 viral vector ameliorates autoimmune demyelination. Hum Gene Ther 1998; 9:2605–2617.

    Article  PubMed  CAS  Google Scholar 

  23. Furlan R, Poliani PL, Marconi PC et al. Central nervous system gene therapy with interleukin-4 inhibits progression of ongoing relapsing-remitting autoimmune encephalomyelitis in Biozzi AB/H mice. Gene Ther 2001; 8:13–19.

    Article  PubMed  CAS  Google Scholar 

  24. Poliani PL, Brok H, Furlan R et al. Delivery to the central nervous system of a nonreplicative herpes simplex type 1 vector engineered with the interleukin 4 gene protects rhesus monkeys from hyperacute autoimmune encephalomyelitis. Hum Gene Ther 2001; 12:905–920.

    Article  PubMed  CAS  Google Scholar 

  25. Lubberts E, Joosten LA, van Den Bersselaar L et al. Adenoviral vector-mediated overexpression of IL-4 in the knee joint of mice with collagen-induced arthritis prevents cartilage destruction. J Immunol 1999; 163:4546–4556.

    PubMed  CAS  Google Scholar 

  26. Woods JM, Katschke KJ, Volin MV et al. IL-4 adenoviral gene therapy reduces inflammation, proinflammatory cytokines, vascularization, and bony destruction in rat adjuvant-induced arthritis. J Immunol 2001; 166:1214–1222.

    PubMed  CAS  Google Scholar 

  27. Lubberts E, Joosten LA, Chabaud M et al. IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion. J Clin Invest 2000; 105:1697–1710.

    PubMed  CAS  Google Scholar 

  28. Boyle DL, Nguyen KH, Zhuang S, Intra-articular IL-4 gene therapy in arthritis: anti-inflammatory effect and enhanced th2activity. Gene Ther 1999; 6:1911–1918.

    Article  PubMed  CAS  Google Scholar 

  29. Cottard V, Mulleman D, Bouille P et al. Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis. Gene Ther 2000; 7:1930–1939.

    Article  PubMed  CAS  Google Scholar 

  30. Morita Y, Yang J, Gupta R et al. Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis. J Clin Invest 2001; 107:1275–1284.

    PubMed  CAS  Google Scholar 

  31. Kim SH, Kim S, Evans CH et al. Effective treatment of established murine collagen-induced ar thritis by systemic administration of dendritic cells genetically modified to express IL-4. J Immunol 2001; 166:3499–3505.

    PubMed  CAS  Google Scholar 

  32. Bessis N, Honiger J, Damotte D et al. Encapsulation in hollow fibres of xenogeneic cells engineered to secrete IL-4 or IL-13 ameliorates murine collagen-induced arthritis (CIA). Clin Exp Immunol 1999; 117:376–382.

    Article  PubMed  CAS  Google Scholar 

  33. Bessis N, Chiocchia G, Kollias G et al. Modulation of proinflammatory cytokine production in tumour necrosis factor-alpha (TNF-alpha)-transgenic mice by treatment with cells engineered to secrete IL-4, IL-10 or IL-13. Clin Exp Immunol 1998; 111:391–396.

    Article  PubMed  CAS  Google Scholar 

  34. Bessis N, Boissier MC, Ferrara P et al. Attenuation of collagen-induced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13. Eur J Immunol 1996; 26:2399–2403.

    PubMed  CAS  Google Scholar 

  35. Tarner IH, Nakajima A, Seroogy CM et al. Retroviral gene therapy of collagen-induced arthritis by local delivery of IL-4. Clin Immunol 2002; 105:304–314.

    Article  PubMed  CAS  Google Scholar 

  36. Zipris D, Karnieli E. A single treatment with IL-4 via retrovirally transduced lymphocytes partially protects against diabetes in BioBreeding (BB) rats. JOP 2002; 3:76–82.

    PubMed  Google Scholar 

  37. Lee M, Koh JJ, Han SO et al. Prevention of autoimmune insulitis by delivery of interleukin-4 plasmid using a soluble and biodegradable polymeric carrier. Pharm Res 2002; 19:246–249.

    Article  PubMed  CAS  Google Scholar 

  38. Goudy K, Song S, Wasserfall C et al. Adeno-associated virus vector-mediated IL-10 gene delivery prevents type 1 diabetes in NOD mice. Proc Natl Acad Sci USA 2001; 98:13913–13918.

    Article  PubMed  CAS  Google Scholar 

  39. Ko KS, Lee M, Koh JJ et al. Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in nonobese diabetic mice. Mol Ther 2001; 4:313–316.

    Article  PubMed  CAS  Google Scholar 

  40. Yamamoto AM, Chernajovsky Y, Lepault F et al. The activity of immunoregulatory T cells mediating active tolerance is potentiated in nonobese diabetic mice by an IL-4-based retroviral gene therapy. J Immunol 2001; 166:4973–4980.

    PubMed  CAS  Google Scholar 

  41. Chang Y, Prud’homme GJ. Intramuscular administration of expression plasmids encoding interferon-gamma receptor/IgG 1 or IL-4/IgG1 chimeric proteins protects from autoimmunity. J Gene Med 1999; 1:415–423.

    Article  PubMed  CAS  Google Scholar 

  42. Mathisen PM, Yu M, Johnson JM et al. Treatment of experimental autoimmune encephalomyelitis with genetically modified memory T cells. J Exp Med 1997; 186:159–164.

    Article  PubMed  CAS  Google Scholar 

  43. Cua DJ, Hutchins B, LaFace DM et al. Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis. J Immunol 2001; 166:602–608.

    PubMed  CAS  Google Scholar 

  44. Croxford JL, Feldmann M, Chernajovsky Y et al. Different therapeutic outcomes in experimental allergic encephalomyelitis dependant upon the mode of delivery of IL-10: a comparison of the effects of protein, adenoviral or retroviral IL-10 delivery into the central nervous system. J Immunol 2001; 166:4124–4130.

    PubMed  CAS  Google Scholar 

  45. Miyata M, Sasajima T, Sato H et al. Suppression of collagen induced arthritis in mice utilizing plasmid DNA encoding interleukin 10. J Rheumatol 2000; 27:1601–1605.

    PubMed  CAS  Google Scholar 

  46. Setoguchi K, Misaki Y, Araki Y et al. Antigen-specific T cells transduced with IL-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen. J Immunol 2000; 165:5980–5986.

    PubMed  CAS  Google Scholar 

  47. Quattrocchi E, Dallman MJ, Dhillon AP et al. Murine IL-10 gene transfer inhibits established collagen-induced arthritis and reduces adenovirus-mediated inflammatory responses in mouse liver. J Immunol 2001; 166:5970–5978.

    PubMed  CAS  Google Scholar 

  48. Saidenberg-Kermanac’h N, Bessis N, Deleuze V et al. Efficacy of interleukin-10 gene electrotransfer into skeletal muscle in mice with collagen-induced arthritis. J Gene Med 2003; 5:164–171.

    Article  PubMed  CAS  Google Scholar 

  49. Zhang YC, Pileggi A, Agarwal A et al. Abstract Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD mice. Diabetes 2003; 52:708–716.

    PubMed  CAS  Google Scholar 

  50. Moritani M, Yoshimoto K, Ii S et al. Prevention of adoptively transferred diabetes in nonobese diabetic mice with IL-10-transduced islet-specific Th1 lymphocytes. A gene therapy model for autoimmune diabetes. J Clin Invest 1996 15;98:1851–1859.

    Google Scholar 

  51. Apparailly F, Verwaerde C, Jacquet C et al. Adenovirus-mediated transfer of viral IL-10 gene inhibits murine collagen-induced arthritis. J Immunol 1998; 160:5213–5220.

    PubMed  CAS  Google Scholar 

  52. Whalen JD, Lechman EL, Carlos CA et al. Adenoviral transfer of the viral IL-10 gene periarticularly to mouse paws suppresses development of collagen-induced arthritis in both injected and uninjected paws. J Immunol 1999; 162:3625–3632.

    PubMed  CAS  Google Scholar 

  53. Lechman ER, Jaffurs D, Ghivizzani SC et al. Direct adenoviral gene transfer of viral IL-10 to rabbit knees with experimental arthritis ameliorates disease in both injected and contralateral control knees. J Immunol 1999; 163:2202–2208.

    PubMed  CAS  Google Scholar 

  54. Ma Y, Thornton S, Duwel LE et al. Inhibition of collagen-induced arthritis in mice by viral IL-10 gene transfer. J Immunol 1998; 161:1516–1524.

    PubMed  CAS  Google Scholar 

  55. Kim SH, Evans CH, Kim S et al. Gene therapy for established murine collagen-induced arthritis by local and systemic adenovirus-mediated delivery of interleukin-4. Arthritis Res 2000; 2:293–302.

    Article  PubMed  CAS  Google Scholar 

  56. Yang Z, Chen M, Wu R et al. Suppression of autoimmune diabetes by viral IL-10 gene transfer. J Immunol 2002; 168:6479–6485.

    PubMed  CAS  Google Scholar 

  57. Nakajima A, Seroogy CM, Sandora MR et al. Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis. J Clin Invest 2001; 107:1293–1301.

    PubMed  CAS  Google Scholar 

  58. Yasuda H, Nagata M, Arisawa K et al. Local expression of immunoregulatory IL-12p40 gene pro longed syngeneic islet graft survival in diabetic NOD mice. J Clin Invest 1998; 102:1807–1814.

    PubMed  CAS  Google Scholar 

  59. Wildbaum G, Netzer N, Karin N. Plasmid DNA encoding IFN-gamma-inducible protein 10 redirects antigen-specific T cell polarization and suppresses experimental autoimmune encephalomyelitis. J Immunol 2002; 168:5885–5892.

    PubMed  CAS  Google Scholar 

  60. Tak PP, Gerlag DM, Aupperle KR et al. Abstract Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation. Arthritis Rheum 2001; 44:1897–1907.

    Article  PubMed  CAS  Google Scholar 

  61. Chen LZ, Hochwald GM, Huang C et al. Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta1. Proc Natl Acad Sci USA 1998; 95:12516–12521.

    Article  PubMed  CAS  Google Scholar 

  62. Song XY, Gu M, Jin WW et al. Plasmid DNA encoding transforming growth factor-beta1 sup presses chronic disease in a streptococcal cell wall-induced arthritis model. J Clin Invest 1998; 101:2615–2621.

    PubMed  CAS  Google Scholar 

  63. Chernajovsky Y, Adams G, Triantaphyllopoulos K et al. Pathogenic lymphoid cells engineered to express TGF beta 1 ameliorate disease in a collagen-induced arthritis model. Gene Ther 1997; 4:553–559.

    Article  PubMed  CAS  Google Scholar 

  64. Piccirillo CA, Chang Y, Prud’homme GJ. TGF-beta1 somatic gene therapy prevents autoimmune disease in nonobese diabetic mice. J Immunol 1998; 161:3950–3956.

    PubMed  CAS  Google Scholar 

  65. Bessis N, Guery L, Mantovani A et al. The type II decoy receptor of IL-1 inhibits murine collagen-induced arthritis. Eur J Immunol 2000; 30:867–875.

    Article  PubMed  CAS  Google Scholar 

  66. Ghivizzani SC, Lechman ER, Kang R et al. Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor alpha soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects. Proc Natl Acad Sci USA 1998; 95:4613–4618.

    Article  PubMed  CAS  Google Scholar 

  67. Prud’homme GJ, Chang Y. et al. Prevention of autoimmune diabetes by intramuscular gene therapy with a nonviral vector encoding an interferon-gamma receptor/IgG1 fusion protein. Gene Ther 1999; 6:771–777.

    Article  PubMed  CAS  Google Scholar 

  68. Quattrocchi E, Walmsley M, Browne K et al. Paradoxical effects of adenovirus-mediated blockade of TNF activity in murine collagen-induced arthritis. J Immunol 1999; 163:1000–1009.

    PubMed  CAS  Google Scholar 

  69. Kolls J, Peppel K, Silva M et al. Prolonged and effective blockade of tumor necrosis factor activity through adenovirus-mediated gene transfer. Proc Natl Acad Sci USA 1994; 91:215–219.

    Article  PubMed  CAS  Google Scholar 

  70. Le CH, Nicolson AG, Morales A et al. Suppression of collagen-induced arthritis through adenovirus-mediated transfer of a modified tumor necrosis factor alpha receptor gene. Arthritis Rheum 1997; 40:1662–1669.

    Article  PubMed  CAS  Google Scholar 

  71. Croxford JL, Triantaphyllopoulos KA, Neve RM et al. Gene therapy for chronic relapsing experimental allergic encephalomyelitis using cells expressing a novel soluble p75 dimeric TNF receptor. J Immunol 2000; 164:2776–2781.

    PubMed  CAS  Google Scholar 

  72. Zhang HG, Xie J, Yang P et al. Adeno-associated virus production of soluble tumor necrosis factor receptor neutralizes tumor necrosis factor alpha and reduces arthritis. Hum Gene Ther 2000; 11:2431–2442.

    Article  PubMed  CAS  Google Scholar 

  73. Chernajovsky Y, Adams G, Podhajcer OL et al. Inhibition of transfer of collagen-induced arthritis into SCID mice by ex vivo infection of spleen cells with retroviruses expressing soluble tumor necrosis factor receptor. Gene Ther 1995; 2:731–735.

    PubMed  CAS  Google Scholar 

  74. Kawaguchi Y. A gene therapy or purified CTLA4IgG treatment of experimental allergic encephalomyelitis. Hokkaido Igaku Zasshi 1999; 74:467–475.

    PubMed  CAS  Google Scholar 

  75. Ijima K, Murakami M, Okamoto H et al. Successful gene therapy via intraarticular injection of adenovirus vector containing CTLA4IgG in a murine model of type II collagen-induced arthritis. Hum Gene Ther 2001; 12:1063–1077.

    Article  PubMed  CAS  Google Scholar 

  76. Wildbaum G, Westermann J, Maor G et al. A targeted DNA vaccine encoding Fas ligand defines its dual role in the regulation of experimental autoimmune encephalomyelitis. J Clin Invest 2000; 106:671–679.

    PubMed  CAS  Google Scholar 

  77. Zhang H, Yang Y, Horton JL et al. Amelioration of collagen-induced arthritis by CD95 (Apo-1/Fas)-ligand gene transfer. J Clin Invest 1997; 100:1951–1957.

    PubMed  CAS  Google Scholar 

  78. Okamoto K, Asahara H, Kobayashi T et al. Induction of apoptosis in the rheumatoid synovium by Fas ligand gene transfer. Gene Ther 1998; 5:331–338.

    Article  PubMed  CAS  Google Scholar 

  79. Contreras JL, Bilbao G, Smyth CA et al. Cytoprotection of pancreatic islets before and early after transplantation using gene therapy. Kidney Int Suppl 2002; 61S1:79–84.

    Article  Google Scholar 

  80. Nasu K, Kohsaka H, Nonomura Y et al. Adenoviral transfer of cyclin-dependent kinase inhibitor genes suppresses collagen-induced arthritis in mice. J Immunol 2000; 165:7246–7252.

    PubMed  CAS  Google Scholar 

  81. Taniguchi K, Kohsaka H, Inoue N et al. Induction of the p16INK4a senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis. Nat Med 1999; 5:760–767.

    Article  PubMed  CAS  Google Scholar 

  82. Goossens PH, Schouten GJ, ’t Hart BA et al. Feasibility of adenovirus-mediated nonsurgical synovectomy in collagen-induced arthritis-affected rhesus monkeys. Hum Gene Ther 1999; 10:1139–1149.

    Article  PubMed  CAS  Google Scholar 

  83. Chen CC, Rivera A, Ron N et al. A gene therapy approach for treating T-cell-mediated autoimmune diseases. Blood 2001; 97:886–894.

    Article  PubMed  CAS  Google Scholar 

  84. Melo ME, Qian J, El-Amine M et al. Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune diseases. J Immunol 2002; 168:4788–4795.

    PubMed  CAS  Google Scholar 

  85. Jun HS, Chung YH, Han J et al. Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase. Diabetologia 2002; 45:668–676.

    Article  PubMed  CAS  Google Scholar 

  86. Melo ME, Qian J, El-Amine M et al. Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune diseases. J Immunol 2002; 168:4788–4795.

    PubMed  CAS  Google Scholar 

  87. Balasa B, Boehm BO, Fortnagel A et al. Vaccination with glutamic acid decarboxylase plasmid DNA protects mice from spontaneous autoimmune diabetes and B7/CD28 costimulation circum vents that protection. Clin Immunol 200; 99:241–252.

    Google Scholar 

  88. Galeano M, Deodato B, Altavilla D et al. Adeno-associated viral vector-mediated human vascular endothelial growth factor gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mouse. Diabetologia 2003 [epub ahead of print].

    Google Scholar 

  89. Mahato RI, Henry J, Narang AS et al. Cationic lipid and polymer-based gene delivery to human pancreatic islets. Mol Ther 2003; 7:89–100.

    Article  PubMed  CAS  Google Scholar 

  90. Romano Di Peppe S, Mangoni A, Zambruno G et al. Adenovirus-mediated VEGF(165) gene transfer enhances wound healing by promoting angiogenesis in CD1 diabetic mice. Gene Ther 2002; 9:1271–1277.

    Article  PubMed  CAS  Google Scholar 

  91. Schratzberger P, Walter DH, Rittig K et al. Reversal of experimental diabetic neuropathy by VEGF gene transfer. J Clin Invest 2001; 107:1083–1092.

    PubMed  CAS  Google Scholar 

  92. Rivard A, Silver M, Chen D et al. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol 1999; 154:355–363.

    PubMed  CAS  Google Scholar 

  93. Mathisen PM, Yu M, Yin L et al. Th2 T cells expressing transgene PDGF-α serve as vectors for gene therapy in autoimmune demyelinating disease. J Autoimm 1999; 3:31–38.

    Article  Google Scholar 

  94. Yamasaki K, Edington HD, McClosky C et al. Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J Clin Invest 1998; 101:967–971.

    PubMed  CAS  Google Scholar 

  95. Ruffini F, Furlan R, Poliani PL et al. Fibroblast growth factor-II gene therapy reverts the clinical course and the pathological signs of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice. Gene Ther 2001; 8:1207–1213.

    Article  PubMed  CAS  Google Scholar 

  96. Giannoukakis N, Mi Z, Rudert WA et al. Prevention of beta cell dysfunction and apoptosis activation in human islets by adenoviral gene transfer of the insulin-like growth factor I. Gene Ther 2000; 7:2015–2022.

    Article  PubMed  CAS  Google Scholar 

  97. Alam T, Sollinger HW. Glucose-regulated insulin production in hepatocytes. Transplantation 2002; 74:1781–1787.

    Article  PubMed  CAS  Google Scholar 

  98. Zhang W, Lu D, Kawazu S et al. Adenoviral Insulin Gene Therapy Prolongs Survival of IDDM Model BB Rats by Improving Hyperlipidemia. Horm Metab Res 2002; 34:577–582.

    Article  PubMed  CAS  Google Scholar 

  99. Martinenghi S, Cusella De Angelis G, Biressi S et al. Human insulin production and amelioration of diabetes in mice by electrotransfer-enhanced plasmid DNA gene transfer to the skeletal muscle. Gene Ther 2002; 9:1429–1437.

    Article  PubMed  CAS  Google Scholar 

  100. Jindal RM, Karanam M, Shah R. Prevention of diabetes in the NOD mouse by intra-muscular injection of recombinant adeno-associated virus containing the preproinsulin II gene. Int J Exp Diabetes Res 2001; 2:129–138.

    PubMed  CAS  Google Scholar 

  101. Auricchio A, Gao GP, Yu QC et al. Constitutive and regulated expression of processed insulin following in vivo hepatic gene transfer. Gene Ther 2002; 9:963–971.

    Article  PubMed  CAS  Google Scholar 

  102. Shaw JA, Delday MI, Hart AW et al. Secretion of bioactive human insulin following plasmid-mediated gene transfer to non-neuroendocrine cell lines, primary cultures and rat skeletal muscle in vivo. J Endocrinol 2002; 172:653–672.

    Article  PubMed  CAS  Google Scholar 

  103. Dong H, Altomonte J, Morral N et al. Basal insulin gene expression significantly improves conventional insulin therapy in type 1 diabetic rats. Diabetes 2002; 51:130–138.

    PubMed  CAS  Google Scholar 

  104. Nagamatsu S, Nakamichi Y, Ohara-Imaizumi M et al. Adenovirus-mediated preproinsulin gene transfer into adipose tissues ameliorates hyperglycemia in obese diabetic KKA(y) mice. FEBS Lett 2001; 509:106–110.

    Article  PubMed  CAS  Google Scholar 

  105. Shifrin AL, Auricchio A, Yu QC et al. Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia. Gene Ther 2001; 8:1480–1489.

    Article  PubMed  CAS  Google Scholar 

  106. Yin D, Tang JG. Gene therapy for streptozotocin-induced diabetic mice by electroporational transfer of naked human insulin precursor DNA into skeletal muscle in vivo. FEBS Lett 2001; 495:16–20.

    Article  PubMed  CAS  Google Scholar 

  107. Chen R, Meseck ML, Woo SL. Auto-regulated hepatic insulin gene expression in type 1 diabetic rats. Mol Ther 2001; 3:584–590.

    Article  PubMed  CAS  Google Scholar 

  108. Chen R, Meseck M, McEvoy RC et al. Glucose-stimulated and self-limiting insulin production by glucose 6-phosphatase promoter driven insulin expression in hepatoma cells. Gene Ther 2000; 7:1802–1809.

    Article  PubMed  CAS  Google Scholar 

  109. Lee HC, Kim SJ, Kim KS et al. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue. Nature 2000; 408:483–488.

    Article  PubMed  CAS  Google Scholar 

  110. Thule PM, Liu JM. Regulated hepatic insulin gene therapy of STZ-diabetic rats. Gene Ther 2000; 7:1744–1752.

    Article  PubMed  CAS  Google Scholar 

  111. Morishita R, Gibbons GH, Kaneda Y et al. Systemic administration of HVJ viral coat-liposome complex containing human insulin vector decreases glucose level in diabetic mouse: A model of gene therapy. Biochem Biophys Res Commun 2000; 273:666–674.

    Article  PubMed  CAS  Google Scholar 

  112. Yamaguchi M, Kuzume M, Matsumoto T et al. Adenovirus-mediated insulin gene transfer improves nutritional and post-hepatectomized conditions in diabetic rats. Surgery 2000; 127:670–678.

    Article  PubMed  CAS  Google Scholar 

  113. Kon OL, Sivakumar S, Teoh KL et al. Naked plasmid-mediated gene transfer to skeletal muscle ameliorates diabetes mellitus. J Gene Med 1999; 1:186–194.

    Article  PubMed  CAS  Google Scholar 

  114. Falqui L, Martinenghi S, Severini GM et al. Reversal of diabetes in mice by implantation of human fibroblasts genetically engineered to release mature human insulin. Hum Gene Ther 1999;10:1753–1762.

    Article  PubMed  CAS  Google Scholar 

  115. Bochan MR, Shah R, Sidner RA et al. Reversal of diabetes in the rat by injection of hematopoietic stem cells infected with recombinant adeno-associated virus containing the preproinsulin II gene. Transplant Proc 1999; 31:690–691.

    Article  PubMed  CAS  Google Scholar 

  116. Shah R, Sidner RA, Bochan MR et al. Reversal of diabetes in streptozotocin-treated rats by intramuscular injection of recombinant adeno-associated virus containing rat preproinsulin II gene. Trans plant Proc 1999; 31:641–642.

    CAS  Google Scholar 

  117. Sugiyama A, Hattori S, Tanaka S et al. Defective adenoassociated viral-mediated transfection of insulin gene by direct injection into liver parenchyma decreases blood glucose of diabetic mice. Horm Metab Res 1997; 29:599–603.

    Article  PubMed  CAS  Google Scholar 

  118. Goldfine ID, German MS, Tseng HC et al. The endocrine secretion of human insulin and growth hormone by exocrine glands of the gastrointestinal tract. Nat Biotechnol 1997; 15:1378–1382.

    Article  PubMed  CAS  Google Scholar 

  119. Kasten-Jolly J, Aubrey MT, Conti DJ et al. Reversal of hyperglycemia in diabetic NOD mice by human proinsulin gene therapy. Transplant Proc 1997; 29:2216–2218.

    Article  PubMed  CAS  Google Scholar 

  120. Kolodka TM, Finegold M, Moss L et al. Gene therapy for diabetes mellitus in rats by hepatic expression of insulin. Proc Natl Acad Sci USA 1995; 92:3293–3297.

    Article  PubMed  CAS  Google Scholar 

  121. Taniguchi H, Nakauchi H, Iwata H et al. Treatment of diabetic mice with encapsulated fibroblasts producing human proinsulin. Transplant Proc 1992; 24:2977–2978.

    PubMed  CAS  Google Scholar 

  122. Kawakami Y, Yamaoka T, Hirochika R et al. Somatic gene therapy for diabetes with an immunological safety system for complete removal of transplanted cells. Diabetes 1992; 41:956–961.

    PubMed  CAS  Google Scholar 

  123. Flugel A, Matsumuro K, Neumann H et al. Anti-inflammatory activity of nerve growth factor in experimental autoimmune encephalomyelitis: inhibition of monocyte transendothelial migration. Eur J Immunol 2001; 31:11–22.

    Article  PubMed  CAS  Google Scholar 

  124. Goss JR, Goins WF, Lacomis D et al. Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse. Dia betes 2002; 51:2227–2232.

    CAS  Google Scholar 

  125. Goins WF, Yoshimura N, Phelan MW et al. Herpes simplex virus mediated nerve growth factor expression in bladder and afferent neurons: potential treatment for diabetic bladder dysfunction. J Urol 2001; 165:1748–1754.

    Article  PubMed  CAS  Google Scholar 

  126. Pradat PF, Kennel P, Naimi-Sadaoui S et al. Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies. Hum Gene Ther 2001; 12:2237–2249.

    Article  PubMed  CAS  Google Scholar 

  127. Taniguchi H, Yamato E, Tashiro F et al. beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther 2003; 10:15–23.

    Article  PubMed  CAS  Google Scholar 

  128. Kojima H, Fujimiya M, Matsumura K, NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 2003; 9:596–603.

    Article  PubMed  CAS  Google Scholar 

  129. Dobrzynski E, Montanari D, Agata J et al. Adrenomedullin improves cardiac function and prevents renal damage in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 2002; 283:E1291–1298.

    PubMed  CAS  Google Scholar 

  130. Morral N, McEvoy R, Dong H et al. Adenovirus-mediated expression of glucokinase in the liver as an adjuvant treatment for type 1 diabetes. Hum Gene Ther 2002; 13:1561–1570.

    Article  PubMed  CAS  Google Scholar 

  131. Emanueli C, Salis MB, Pinna A et al. Prevention of diabetes-induced microangiopathy by human tissue kallikrein gene transfer. Circulation 2002; 106:993–999.

    Article  PubMed  CAS  Google Scholar 

  132. Slosberg ED, Desai UJ, Fanelli B et al. Treatment of type 2 diabetes by adenoviral-mediated overexpression of the glucokinase regulatory protein. Diabetes 2001; 50:1813–1820.

    PubMed  CAS  Google Scholar 

  133. Ozawa K, Kondo T, Hori O et al. Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport. J Clin Invest 2001; 108:41–50.

    Article  PubMed  CAS  Google Scholar 

  134. Ueki K, Yamauchi T, Tamemoto H et al. Restored insulin-sensitivity in IRS-1-deficient mice treated by adenovirus-mediated gene therapy. J Clin Invest 2000; 105:1437–1445.

    PubMed  CAS  Google Scholar 

  135. Yamasaki K, Edington HD, McClosky C et al. Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J Clin Invest 1998; 101:967–971.

    Article  PubMed  CAS  Google Scholar 

  136. Murphy JE, Zhou S, Giese K et al. Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin. Proc Natl Acad Sci USA 1997; 94:13921–13926.

    Article  PubMed  CAS  Google Scholar 

  137. Muzzin P, Eisensmith RC, Copeland KC et al. Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. Proc Natl Acad Sci USA 1996; 93:14804–14808.

    Article  PubMed  CAS  Google Scholar 

  138. van der Laan WH, Quax PH, Seemayer CA et al. Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of TIMP-1 and TIMP-3. Gene Ther 2003; 10:234–242.

    Article  PubMed  CAS  Google Scholar 

  139. Martino G, Furlan R, Comi G et al. The ependymal route to the CNS: an emerging gene-therapy approach for MS. Trends Immunol 2001; 22:483–490.

    Article  PubMed  CAS  Google Scholar 

  140. http://www.wiley.co.uk/wileychi/genmed/clinical/, trial no. 357.

    Google Scholar 

  141. http://www.wiley.co.uk/wileychi/genmed/clinical/, trial no. 627.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology and Neurophysiology, Neuroimmunology Unit-DIBIT, San Raffaele Scientific Instituite, Via Olgettina 58, 20132, Milan, Italy

    Roberto Furlan

  2. Neuroimmunology Unit-DIBIT Department of Neurology and Neurophysiology, San Raffaele Scientific Institute, Milan, Italy

    Erica Butti, Stefano Pluchino & Gianvito Martino

Authors
  1. Roberto Furlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erica Butti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefano Pluchino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gianvito Martino
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Eurekah.com and Kluwer Academic / Plenum Publishers

About this chapter

Cite this chapter

Furlan, R., Butti, E., Pluchino, S., Martino, G. (2005). Gene Therapy Approaches for Autoimmune Diseases of the Central Nervous System and Other Tissues. In: Gene Therapy of Autoimmune Diseases. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-28670-5_1

Download citation

Publish with us

Policies and ethics

Search

Navigation