The therapeutic use of gene therapy in inflammatory demyelinating diseases of the central nervous system

Current Opinion in Neurology

Volumn 16, Issue 3, 2003, Pages 385-392

  Furlan, Roberto ^a   Pluchino, Stefano ^a   Martino, Gianvito ^a  

^a SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

Demyelination; Gene therapy; Inflammation; Multiple sclerosis; Neuroprotection

Indexed keywords

BETA INTERFERON; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DNA; FAS ANTIGEN; FIBROBLAST GROWTH FACTOR 2; GAMMA INTERFERON; GROWTH FACTOR; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; LIPOSOME; MYELIN; MYELIN BASIC PROTEIN; NERVE GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR A; PROTEIN P55; PROTEIN P75; RETROVIRUS VECTOR; TUMOR NECROSIS FACTOR ALPHA;

B LYMPHOCYTE; BLOOD BRAIN BARRIER; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; DNA VECTOR; GENE TARGETING; GENE THERAPY; GENETIC ENGINEERING; GENETIC TRANSFECTION; INHIBITION KINETICS; MONKEY; MULTIPLE SCLEROSIS; NONHUMAN; OLIGODENDROGLIA; REMYELINIZATION; REVIEW; TREATMENT OUTCOME;

ANIMALS; ANTI-INFLAMMATORY AGENTS; CENTRAL NERVOUS SYSTEM DISEASES; DEMYELINATING DISEASES; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; GENE THERAPY; HUMANS; IMMUNOTHERAPY; INFLAMMATION; MULTIPLE SCLEROSIS; NERVE GROWTH FACTORS;

EID: 0037782146     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/00019052-200306000-00020     Document Type: Review

References (47)

1. Martino G, Hartung HP. Immunopathogenesis of multiple sclerosis: the role of T cells. Curr Opin Neurol 1999; 12:309-321.
2. Kieseier BC, Storch MK, Archelos JJ, et al. Effector pathways in immune mediated central nervous system demyelination. Curr Opin Neurol 1999; 12:323-336.
3. Martino G, Adorini L, Rieckmann P, et al. Inflammation in multiple sclerosis: the good, the bad, and the complex. Lancet Neurol 2002; 1:499-509. A comprehensive review dealing with the apparently contradictory role played by inflammation in MS.
4. Franklin RJ. Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci 2002; 3:705-714. A complete review dealing with one of the most difficutt challenges in multiple sclerosis. The topic, which is discussed and analysed in detail, provides realistic explanations for the failure of remyelination in MS and suggests strategies for successful remyelination.
5. The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis: I. Clinical results of a multicenter, randomized, double-blind, placebo, controlled trial. Neurology 1993; 43:655-661.
6. Calabresi PA, Fields NS, Maloni HW, et al. Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS. Neurology 1998; 51:289-292.
7. The Lenercept Multiple Sclerosis Study Group and University of British Columbia MS/MRI Analysis Group. TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 1999; 53:457-465.
8. van Oosten BW, Barkhof F, Truyen L, et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 1996; 47:1531-1534.
9. Saunders NR, Habgood MD, Dziegielewska KM. Barrier mechanisms in the brain: I. Adult brain. Clin Exp Pharmaccl Physiol 1999; 26:11-19.
10. 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.
11. 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.
12. Willenborg DO, Fordham SA, Cowden WB, Ramshaw IA. 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.
13. Fudan 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. The unexpected and challenging demonstration that a proinflammatory cytokine, such as IFNγ, may be beneficial in EAE when delivered in the CNS using a gene therapy protocol.
14. 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.
15. Dal Canto RA, Shaw MK, Nolan GP, et al. Local delivery of TNF by retrovirus-transduced T lymphocytes exacerbates experimental autoimmune encephalomyelitis. Clin Immunol 1999; 90:10-14.
16. 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.
17. 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. The paper clearly demonstrates that the co-delivery of the IL-4 gene and of a DNA vaccine encoding the self-peptide PLP139-151 provides protective immunity against EAE. This is a very interesting work suggesting a possible, although futuristic, combination therapy for multiple sclerosis.
18. Broberg E, Set ala 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.
19. 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.
20. Furlan R, Poliani PL, Marconi PC, et al. Central nervous system gene therapy with interleukin-4 inhibits progression of ongoing relapsing-remitting auto-immune encephalomyelitis in Biozzi AB/H mice. Gene Ther 2001; 8:13-19
21. Poliani PL, Brok H, Fudan 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. The first successful gene therapy protocol in a non-human primate model of MS based on the intrathecal delivery of the gene coding for the prototypical antiinflammatory cytokine IL-4 using HSV-l-derived viral vectors.
22. 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.
23. Cua DJ, Hutchins B, LaFace DM, et al. Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis. J Immunol 2001; 166:602-608.
24. Croxford JL, Feldmann M, Chernajovsky Y, Baker D. Different therapeutic outcomes in experimental allergic encephalomyelitis dependent 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. An interesting work aimed to compare different gene therapy approaches to deliver the antiinflammatory IL-10 gene within the CNS of EAE mice.
25. 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.
26. 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. The first gene therapy protocol in EAE aimed to therapeutically target a potential detrimental chemokine.
27. Kawaguchi Y. A gene therapy or purified CTLA41gG treatment of experimental allergic encephalomyelitis. Hokkaido Igaku Zasshi 1999; 74:467-475.
28. Wildbaum G, Westermann J, Maor G, Karin N. 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.
29. Chen CC, Rivera A, Ron N, et al. A gene therapy approach for treating T-cell-mediated autoimmune diseases. Blood 2001; 97:886-894. The first approach in EAE based on the use of engineered B cells as tolerogenic agents. Retroviraily transfected B cells deliver an anergic signal to encephalitogenic T cell thus preventing EAE onset.
30. 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. One of the first attempts to use genetically modified B cells as tolerogenic agents in autoimmunity. This protocol determined the amelioration of ongoing EAE.
31. 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 Autoimmun 1999; 3:31-38.
32. 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. The first gene therapy protocol based on the CNS delivery of a growth factor showing efficacy to both dampen inflammation and foster remyelination in rodent EAE.
33. 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 U S A 1998; 95:12516-12521.
34. 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.
35. Triantaphyllopoulos K, Croxford J, Baker D, Chernajovsky Y. Cloning and expression of murine IFN beta and a TNF antagonist for gene therapy of experimental allergic encephalomyelitis. Gene Ther 1998; 5:253-263.
36. Martino G, Furlan R, Comi G, Adorini L. The ependymal route to the CNS: an emerging gene-therapy approach for MS. Trends Immunol 2001; 22:483-490. A point of view describing in detail the 'ependymal route' as an alternative and feasible way to approach cytokine-gene therapy in EAE/MS.
37. Akli S, Caillaud C, Vigne E, et al. Transfer of a foreign gene into the brain using adenovirus vectors. Nat Genet 1993; 3:224-228.
38. Bajocchi G, Feldman SH, Crystal RG, Mastrangeli A. Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors. Nat Genet 1993; 3:229-234.
39. Ohashi T, Watabe K, Uehara K, et al. Adenovirus-mediated gene transfer and expression of human β-glucuronidase gene in the liver, spleen, and central nervous system in mucopolysaccharidosis type VII mice. Proc Natl Acad Sci U S A 1997; 94:1287-1292.
40. Driesse MJ, Kros JM, Avezaat CJ, et al. Distribution of recombinant adenovirus in the cerebrospinal fluid of non-human primates. Hum Gene Ther 1999; 10:2347-2354.
41. Frank JA, Richert N, Lewis B, et al. A pilot study of recombinant insulin-like growth factor-1 in seven multiple sclerosis patients. Mult Scler 2002; 8:24-29.
42. Bielekova B, Goodwin B, Richert N, et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat Med 2000; 6:1167-1175.
43. Kappos L, Comi G, Panitch H, et al. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group. Nat Med 2000; 6:1176-1182.
44. Tsunoda I, Tolley ND, Theil DJ, et al. Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA. Brain Pathol 1999; 9:481-493.
45. Boccaccio GL, Mor F, Steinman L. Non-coding plasmid DNA induces IFN-gamma in vivo and suppresses autoimmune encephalomyelitis. Int Immunol 1999; 11:289-296.
46. 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.
47. Thomas CE, Schiedner G, Kochanek S, et al. Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors; toward realistic long-term neurological gene therapy for chronic diseases. Proc Natl Acad Sci U S A 2000; 97:7482-7487.