Gene therapy in Parkinson's disease

Cell and Tissue Research

Volumn 318, Issue 1, 2004, Pages 243-260

  Eberhardt, O ^a   Schulz, J B ^a  

^a UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

Animal models; Gene therapy; Parkinson's disease

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; 4 AMINOBUTYRIC ACID; ADENOVIRUS VECTOR; APOMORPHINE; APOPTOTIC PROTEASE ACTIVATING FACTOR 1; CALPAIN; CALPASTATIN; CASPASE 3; CASPASE 9; CYCLIN DEPENDENT KINASE 5; DOPAMINE; FREE RADICAL; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; HERPESVIRUS VECTOR; LENTIVIRUS VECTOR; LEVODOPA; MESSENGER RNA; NEUROTOXIN; OXIDOPAMINE; PARVOVIRUS VECTOR; PROTEIN BCL 2; RECOMBINANT GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; RETROVIRUS VECTOR; STRESS ACTIVATED PROTEIN KINASE; TRANSFORMING GROWTH FACTOR BETA; TYROSINE 3 MONOOXYGENASE; UNCLASSIFIED DRUG; X LINKED INHIBITOR OF APOPTOSIS;

ANIMAL CELL; ANIMAL MODEL; BASAL GANGLION; BRAIN DEPTH STIMULATION; CLINICAL ARTICLE; DOPAMINE RELEASE; GENE THERAPY; GENE TRANSFER; HUMAN; NEUROLOGIC DISEASE; NEUROTRANSMITTER RELEASE; NONHUMAN; NONVIRAL GENE THERAPY; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REVIEW; SIGNAL TRANSDUCTION; SUBSTANTIA NIGRA; SUBTHALAMIC NUCLEUS; VIRAL GENE THERAPY;

ADENOVIRIDAE; ANIMALIA; HERPESVIRIDAE; LENTIVIRUS; PARVOVIRUS; UNIDENTIFIED RETROVIRUS;

EID: 5444265882     PISSN: 0302766X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00441-004-0947-x     Document Type: Review

References (176)

1. Akerud P, Canals JM, Snyder EY, Arenas E (2001) Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson's disease. J Neurosci 21:8108-8118
2. Akli S, Caillaud C, Vigne E, Stratford-Perricaudet LD, Poenaru L, Perricaudet M, Kahn A, Peschanski MR (1993) Transfer of a foreign gene into the brain using adenovirus vectors. Nat Genet 3:224-228
3. Anton R, Kordower JH, Kane DJ, Markham CH, Bredesen DE (1995) Neural transplantation of cells expressing the anti-apoptotic gene bcl-2. Cell Transplant 4:49-54
4. Asanuma M, Hirata H, Cadet JL (1998) Attenuation of 6-hydroxydopamine- induced dopaminergic nigrostriatal lesions in superoxide dismutase transgenic mice. Neuroscience 85:907-917
5. Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM (2002) Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295:865-868
6. Azzouz M, Martin-Rendon E, Barber RD, Mitrophanous KA, Carter EE, Rohll JB, Kingsman SM, Kingsman AJ, Mazarakis ND (2002) Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson's disease. J Neurosci 22:10302-10312
7. Azzouz M, Ralph S, Wong LF, Day D, Askham Z, Barber RD, Mitrophanous KA, Kingsman SM, Mazarakis ND (2004) Neuroprotection in a rat Parkinson model by GDNF gene therapy using EIAV vector. Neuroreport 15:985-990
8. Bankiewicz KS, Leff SE, Nagy D, Jungles S, Rokovitch J, Spratt K, Cohen L, Libonati M, Snyder RO, Mandel RJ (1997) Practical aspects of the development of ex vivo and in vivo gene therapy for Parkinson's disease. Exp Neurol 144:147-156
9. Bankiewicz KS, Eberling JL, Kohutnicka M, Jagust W, Pivirotto P, Bringas J, Cunningham J, Budinger TF, Harvey-White J (2000) Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol 164:2-14
10. Bankiewicz KS, Daadi M, Pivirotto P, Bringas J, Sanchez-Pernaute R, Herscovitch P, et al (2003) Long term evaluation of AAV/AADC gene transfer in parkinsonian monkeys. Program no. 229.14.2003 abstract viewer/itinerary planner. Society for Neuroscience, Washington DC
11. Barkats M, Nakao N, Grasbon-Frodl EM, Bilang-Bleuel A, Revah F, Mallet J, Brundin P (1997) Intrastriatal grafts of embryonic mesencephalic rat neurons genetically modified using an adenovirus encoding human Cu/Zn superoxide dismutase. Neuroscience 78:703-713
12. Barkats M, Millecamps S, Bilang-Bleuel A, Mallet J (2002) Neuronal transfer of the human Cu/Zn superoxide dismutase gene increases the resistance of dopaminergic neurons to 6-hydroxydopamine. J Neurochem 82:101-109
13. Barker R, Dunnett SB (1994) Ibotenic acid lesions of the striatum reduce drug-induced rotation in the 6-hydroxydopamine-lesioned rat. Exp Brain Res 101:365-374
14. Baumgartner BJ, Shine HD (1997) Targeted transduction of CNS neurons with adenoviral vectors carrying neurotrophic factor genes confers neuroprotection that exceeds the transduced population. J Neurosci 17:6504-6511
15. Bencsics C, Wachtel SR, Milstien S, Hatakeyama K, Becker JB, Kang UJ (1996) Double transduction with GTP cyclohydrolase I and tyrosine hydroxylase is necessary for spontaneous synthesis of L-DOPA by primary fibroblasts. J Neurosci 16:4449-4456
16. Bensadoun JC, Deglon N, Tseng JL, Ridet JL, Zurn AD, Aebischer P (2000) Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson's disease using GDNF. Exp Neurol 164:15-24
17. Bilang-Bleuel A, Revah F, Colin P, Locquet I, Robert JJ, Mallet J, Horellou P (1997) Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease. Proc Natl Acad Sci USA 94:8818-8823
18. Björklund A, Lindvall O (2000) Parkinson disease gene therapy moves toward the clinic. Nat Med 6:1207-1208
19. Björklund A, Kirik D, Rosenblad C, Georgievska B, Lundberg C, Mandel RJ (2000) Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res 886:82-98
20. Bohn MC, Choi-Lundberg DL, Davidson BL, Leranth C, Kozlowski DA, Smith JC, O'Banion MK, Redmond DE Jr (1999) Adenovirus-mediated transgene expression in nonhuman primate brain. Hum Gene Ther 10:1175-1184
21. Bowenkamp KE, Hoffman AF, Gerhardt GA, Henry MA, Biddle PT, Koffer BJ, Granholm AC (1995) Glial cell line-derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons. J Comp Neurol 355:479-489
22. Burton EA, Glorioso JC, Fink DJ (2003) Gene therapy progress and prospects: Parkinson's disease. Gene Ther 10:1721-1727
23. Byrnes AP, Rusby JE, Wood MJ, Charlton HM (1995) Adenovirus gene transfer causes inflammation in the brain. Neuroscience 66:1015-1024
24. Byrnes AP, Mac Laren RE, Charlton HM (1996) Immunological instability of persistent adenovirus vectors in the brain: peripheral exposure to vector leads to renewed inflammation, reduced gene expression, and demyelination. J Neurosci 16:3045-3055
25. Cao L, Zhao YC, Jiang ZH, Xu DH, Liu ZG, Chen SD, Liu XY, Zheng ZC (2000) Long-term phenotypic correction of rodent hemiparkinsonism by gene therapy using genetically modified myoblasts. Gene Ther 1:445-449
26. Cartmell T, Southgate T, Rees GS, Castro MG, Lowenstein PR, Luheshi GN (1999) Interleukin-1 mediates a rapid inflammatory response after injection of adenoviral vectors into the brain. J Neurosci 19:1517-1523
27. Casper D, Engstrom SJ, Mirchandani GR, Pidel A, Palencia D, Cho PH, Brownlee M, Edelstein D, Federoff HJ, Sonstein WJ (2002) Enhanced vascularization and survival of neural transplants with ex vivo angiogenic gene transfer. Cell Transplant 11:331-349
28. Chang JW, Lee WY, Milstien S, Kang UJ (2002) A site-specific mutation of tyrosine hydroxylase reduces feedback inhibition by dopamine in genetically modified cells grafted in parkinsonian rats. J Neurochem 83:141-149
29. Chen S, Xianwen C, Dehua X, Zhenguo L, Lingfei X, Smith SW, Zhongcheng Z (2003) Behavioral correction of parkinsonian rats following the transplantation of immortalized fibroblasts genetically modified with TH and GCH genes. Parkinsonism Relat Disord 9 (Suppl 2):S91-S97
30. Choi-Lundberg DL, Lin Q, Chang YN, Chiang YL, Hay CM, Mohajeri H, Davidson BL, Bohn MC (1997) Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 275:838-841
31. Choi-Lundberg DL, Lin Q, Schallert T, Crippens D, Davidson BL, Chang YN, Chiang YL, Qian J, Bardwaj L, Bohn MC (1998) Behavioral and cellular protection of rat dopaminergic neurons by an adenoviral vector encoding glial cell line-derived neurotrophic factor. Exp Neurol 154:261-275
32. Coelln R von, Kugler S, Bahr M, Weller M, Dichgans J, Schulz JB (2001) Rescue from death but not from functional impairment: caspase inhibition protects dopaminergic cells against 6-hydroxydopamine-induced apoptosis but not against the loss of their terminals. J Neurochem 77:263-273
33. Connor B, Kozlowski DA, Schallert T, Tillerson JL, Davidson BL, Bohn MC (1999) Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged parkinsonian rat. Gene Ther 6:1936-1951
34. Connor B, Kozlowski DA, Unnerstall JR, Elsworth JD, Tillerson JL, Schallert T, Bohn MC (2001) Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects dopaminergic terminals from degeneration. Exp Neurol 169:83-95
35. Cortez N, Trejo F, Vergara P, Segovia J (2000) Primary astrocytes retrovirally transduced with a tyrosine hydroxylase transgene driven by a glial-specific promoter elicit behavioral recovery in experimental parkinsonism. J Neurosci Res 59:39-46
36. Corti O, Sanchez-Capelo A, Colin P, Hanoun N, Hamon M, Mallet J (1999) Long-term doxycycline-controlled expression of human tyrosine hydroxylase after direct adenovirus-mediated gene transfer to a rat model of Parkinson's disease. Proc Natl Acad Sci USA 96:12120-12125
37. Costantini LC, Jacoby DR, Wang S, Fraefel C, Breakefield XO, Isacson O (1999) Gene transfer to the nigrostriatal system by hybrid Herpes simplex virus/adeno-associated virus amplicon vectors. Hum Gene Ther 10:2481-2494; Erratum (2000) 11:981
38. Crocker SJ, Wigle N, Liston P, Thompson CS, Lee CJ, Xu D, Roy S, Nicholson DW, Park DS, MacKenzie A, Korneluk RG, Robertson GS (2001) NAIP protects the nigrostriatal dopamine pathway in an intrastriatal 6-OHDA rat model of Parkinson's disease. Eur J Neurosci 14:391-400
39. Crocker SJ, Smith PD, Jackson-Lewis V, Lamba WR, Hayley SP, Grimm E, Callaghan SM, Slack RS, Melloni E, Przedborski S, Robertson GS, Anisman H, Merali Z, Park DS (2003) Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson's disease. J Neurosci 23:4081-4091
40. Cunningham LA, Su C (2002) Astrocyte delivery of glial cell line-derived neurotrophic factor in a mouse model of Parkinson's disease. Exp Neurol 174:230-242
41. Cunningham LA, Short MP, Breakefield XO, Bohn MC (1994) Nerve growth factor released by transgenic astrocytes enhances the function of adrenal chromaffin cell grafts in a rat model of Parkinson's disease. Brain Res 658:219-231
42. Davidson BL, Breakefield XO (2003) Viral vectors for gene delivery to the nervous system. Nat Rev Neurosci 4:353-364
43. Davidson BL, Allen ED, Kozarsky KF, Wilson JM, Roessler BJ (1993) A model system for in vivo gene transfer into the central nervous system using an adenoviral vector. Nat Genet 3:219-223
44. Deglon N, Tseng JL, Bensadoun JC, Zurn AD, Arsenijevic Y, Pereira de Almeida L, Zufferey R, Trono D, Aebischer P (2000) Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson's disease. Hum Gene Ther 11:179-190
45. Deumens R, Blokland A, Prickaerts J (2002) Modeling Parkinson's disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 175:303-317
46. Dewey RA, Morrissey G, Cowsill CM, Stone D, Bolognani F, Dodd NJ, Southgate TD, Klatzmann D, Lassmann H, Castro MG, Lowenstein PR (1999) Chronic brain inflammation and persistent Herpes simplex virus 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: implications for clinical trials. Nat Med 5:1256-1263
47. Do Thi NA, Saillour P, Ferrero L, Dedieu JF, Mallet J, Paunio T (2004) Delivery of GDNF by an E1,E3/E4 deleted adenoviral vector and driven by a GFAP promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson's disease. Gene Ther (in press)
48. Dunnett SB, Björklund A (1999) Prospects for new restorative and neuroprotective treatments in Parkinson's disease. Nature 399 (6738 Suppl):A32-A39
49. During MJ, Naegele JR, O'Malley KL, Geller AI (1994) Long-term behavioral recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylase. Science 266:1399-1403
50. During MJ, Samulski RJ, Elsworth JD, Kaplitt MG, Leone P, Xiao X, Li J, Freese A, Taylor JR, Roth RH, Sladek JR Jr, O'Malley KL, Redmond DE Jr (1998) In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector. Gene Ther 5:820-827
51. During MJ, Kaplitt MG, Stern MB, Eidelberg D (2001) Subthalamic GAD gene transfer in Parkinson disease patients who are candidates for deep brain stimulation. Hum Gene Ther 12:1589-1591
52. Eberhardt O, Schulz JB (2003) Apoptotic mechanisms and antiapoptotic therapy in the MPTP model of Parkinson's disease. Toxicol Lett 139:135-151
53. Eberhardt O, Coelln RV, Kugler S, Lindenau J, Rathke-Hartlieb S, Gerhardt E, Haid S, Isenmann S, Gravel C, Srinivasan A, Bahr M, Weller M, Dichgans J, Schulz JB (2000) Protection by synergistic effects of adenovirus-mediated X-chromosome-linked inhibitor of apoptosis and glial cell line-derived neurotrophic factor gene transfer in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine model of Parkinson's disease. J Neurosci 20:9126-9134
54. Eberling JL, Cunningham J, Pivirotto P, Bringas J, Daadi MM, Bankiewicz KS (2003) In vivo PET imaging of gene expression in parkinsonian monkeys. Mol Ther 8:873-875
55. Ericson C, Wictorin K, Lundberg C (2002) Ex vivo and in vitro studies of transgene expression in rat astrocytes transduced with lentiviral vectors. Exp Neurol 173:22-30
56. Eslamboli A, Cummings RM, Ridley RM, Baker HF, Muzyczka N, Burger C, Mandel RJ, Kirik D, Annett LE (2003) Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides protection against 6-OHDA lesion in the common marmoset monkey (Callithrix jacchus). Exp Neurol 184:536-548
57. Fan DS, Ogawa M, Fujimoto KI, Ikeguchi K, Ogasawara Y, Urabe M, Nishizawa M, Nakano I, Yoshida M, Nagatsu I, Ichinose H, Nagatsu T, Kurtzman GJ, Ozawa K (1998) Behavioral recovery in 6-hydroxydopamine-lesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate adeno-associated virus vectors. Hum Gene Ther 9:2527-2535
58. Fink DJ, Glorioso J, Mata M (2003) Therapeutic gene transfer with Herpes-based vectors: studies in Parkinson's disease and motor nerve regeneration. Exp Neurol 184 (Suppl 1):S19-S24
59. Fitoussi N, Sotnik-Barkai I, Tornatore C, Herzberg U, Yadid G (1998) Dopamine turnover and metabolism in the striatum of parkinsonian rats grafted with genetically-modified human astrocytes. Neuroscience 85:405-413
60. Frim DM, Uhler TA, Galpern WR, Beal MF, Breakefield XO, Isacson O (1994) Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc Natl Acad Sci USA 91:5104-5108
61. Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russell D, Martin D, Lapchak PA, Collins F, Hoffer BJ, Gerhardt GA (1996) Functional recovery in parkinsonian monkeys treated with GDNF. Nature 380:252-255
62. Gash DM, Zhang Z, Gerhardt G (1998) Neuroprotective and neurorestorative properties of GDNF. Ann Neurol 44 (3 Suppl 1):S121-S125
63. Georgievska B, Kirik D, Björklund A (2002a) Aberrant sprouting and downregulation of tyrosine hydroxylase in lesioned nigrostriatal dopamine neurons induced by long-lasting overexpression of glial cell line derived neurotrophic factor in the striatum by lentiviral gene transfer. Exp Neurol 177:461-474
64. Georgievska B, Kirik D, Rosenblad C, Lundberg C, Björklund A (2002b) Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector. Neuroreport 13:75-82
65. Gerin C (2002) Behavioral improvement and dopamine release in a parkinsonian rat model. Neurosci Lett 330:5-8
66. Gill SS, Patel NK, Hotton GR, O'Sullivan K, McCarter R, Bunnage M, Brooks DJ, Svendsen CN, Heywood P (2003) Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 9:589-595
67. Golden JP, Baloh RH, Kotzbauer PT, Lampe PA, Osborne PA, Milbrandt J, Johnson EM Jr (1998) Expression of neurturin, GDNF, and their receptors in the adult mouse CNS. J Comp Neurol 398:139-150
68. Hagihara Y, Saitoh Y, Kaneda Y, Kohmura E, Yoshimine T (2000) Widespread gene transfection into the central nervous system of primates. Gene Ther 7:759-763
69. Harui A, Suzuki S, Kochanek S, Mitani K (1999) Frequency and stability of chromosomal integration of adenovirus vectors. J Virol 73:6141-6146
70. Hayley S, Crocker SJ, Smith PD, Shree T, Jackson-Lewis V, Przedborski S, Mount M, Slack R, Anisman H, Park DS (2004) Regulation of dopaminergic loss by Fas in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. J Neurosci 24:2045-2053
71. Hermens WT, Verhaagen J (1998) Viral vectors, tools for gene transfer in the nervous system. Prog Neurobiol 55:399-432
72. Hida H, Hashimoto M, Fujimoto I, Nakajima K, Shimano Y, Nagatsu T, Mikoshiba K, Nishino H (1999) Dopa-producing astrocytes generated by adenoviral transduction of human tyrosine hydroxylase gene: in vitro study and transplantation to hemiparkinsonian model rats. Neurosci Res 35:101-112
73. Horellou P, Mallet J (1997) Gene therapy for Parkinson's disease. Mol Neurobiol 15:241-256
74. Horellou P, Vigne E, Castel MN, Barneoud P, Colin P, Perricaudet M, Delaere P, Mallet J (1994) Direct intracerebral gene transfer of an adenoviral vector expressing tyrosine hydroxylase in a rat model of Parkinson's disease. Neuroreport 6:49-53
75. Howard K (2003) First Parkinson gene therapy trial launches. Nat Biotechnol 21:1117-1118
76. Hsich G, Sena-Esteves M, Breakefield XO (2002) Critical issues in gene therapy for neurologic disease. Hum Gene Ther 13:579-604
77. Hurelbrink CB, Barker RA (2004) The potential of GDNF as a treatment for Parkinson's disease. Exp Neurol 185:1-6
78. Ikari H, Zhang L, Chernak JM, Mastrangeli A, Kato S, Kuo H, Crystal RG, Ingram DK, Roth GS (1995) Adenovirus-mediated gene transfer of dopamine D2 receptor cDNA into rat striatum. Brain Res Mol Brain Res 34:315-320
79. Imaoka T, Date I, Ohmoto T, Nagatsu T (1998) Significant behavioral recovery in Parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid DNA-liposome complex. Hum Gene Ther 9:1093-1102
80. Isacson O (1995) Behavioral effects and gene delivery in a rat model of Parkinson's disease. Science 269:856-857
81. Jiang C, Koyabu N, Yonemitsu Y, Shimazoe T, Watanabe S, Naito M, Tsuruo T, Ohtani H, Sawada Y (2003) In vivo delivery of glial cell-derived neurotrophic factor across the blood-brain barrier by gene transfer into brain capillary endothelial cells. Hum Gene Ther 14:1181-1191
82. Jiao S, Gurevich V, Wolff JA (1996) Long-term correction of rat nmodel of Parkinson's disease by gene therapy. Nature 362:450-453 (Retracted by Wolff JA, 1996, Nature 380:734)
83. Jiao S, Gurevich V, Wolff JA (1996) Long-term correction of rat nmodel of Parkinson's disease by gene therapy. Nature 362:450-453 (Retracted by Wolff JA, 1996, Nature 380:734)
84. Kajiwara K, Byrnes AP, Charlton HM, Wood MJ, Wood KJ (1997) Immune responses to adenoviral vectors during gene transfer in the brain. Hum Gene Ther 8:253-265
85. Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, Boonplueang R, Viswanath V, Jacobs R, Yang L, Beal MF, DiMonte D, Volitaskis I, Ellerby L, Cherny RA, Bush AI, Andersen JK (2003) Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron 37:899-909
86. Kennedy PG (1997) Potential use of Herpes simplex virus (HSV) vectors for gene therapy of neurological disorders. Brain 120:1245-1259
87. Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418:50-56
88. Kirik D, Björklund A (2003) Modeling CNS neurodegeneration by overexpression of disease-causing proteins using viral vectors. Trends Neurosci 26:386-392
89. Kirik D, Rosenblad C, Björklund A, Mandel RJ (2000) Long-term rAAV-mediated gene transfer of GDNF in the rat Parkinson's model: intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system. J Neurosci 20:4686-4700
90. Kirik D, Georgievska B, Burger C, Winkler C, Muzyczka N, Mandel RJ, Björklund A (2002) Reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of L-dopa using rAAV-mediated gene transfer. Proc Natl Acad Sci USA 99:4708-4713
91. Kirik D, Georgievska B, Björklund A (2004) Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nat Neurosci 7:105-110
92. Klein RL, Lewis MH, Muzyczka N, Meyer EM (1999) Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer. Brain Res 847:314-320
93. Kojima H, Abiru Y, Sakajiri K, Watabe K, Ohishi N, Takamori M, Hatanaka H, Yagi K (1997) Adenovirus-mediated transduction with human glial cell line-derived neurotrophic factor gene prevents 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced dopamine depletion in striatum of mouse brain. Biochem Biophys Res Commun 238:569-573
94. Kordower JH (2003) In vivo gene delivery of glial cell line-derived neurotrophic factor for Parkinson's disease. Ann Neurol 53 (Suppl 3):S120-S132
95. Kordower JH, Bloch J, Ma SY, Chu Y, Palfi S, Roitberg BZ, Emborg M, Hantraye P, Deglon N, Aebischer P (1999) Lentiviral gene transfer to the nonhuman primate brain. Exp Neurol 160:1-16
96. Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Deglon N, Aebischer P (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 290:767-773
97. Kozlowski DA, Connor B, Tillerson JL, Schallen T, Bohn MC (2000) Delivery of a GDNF gene into the substantia nigra after a progressive 6-OHDA lesion maintains functional nigrostriatal connections. Exp Neurol 166:1-15
98. Kroll RA, Neuwelt EA (1998) Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery 42:1083-1099 (discussion 1099-1100)
99. Lapchak PA, Araujo DM, Hilt DC, Sheng J, Jiao S (1997) Adenoviral vector-mediated GDNF gene therapy in a rodent lesion model of late stage Parkinson's disease. Brain Res 777:153-160
100. Le HN, Frim DM (2002) Gene therapy for Parkinson's disease. Expert Opin Biol Ther 2:151-161
101. Lee WY, Chang JW, Nemeth NL, Kang UJ (1999) Vesicular monoamine transporter-2 and aromatic L-amino acid decarboxylase enhance dopamine delivery after L-3, 4-dihydroxyphenylalanine administration in parkinsonian rats. J Neurosci 19:3266-3274
102. Leff SE, Spratt SK, Snyder RO, Mandel RJ (1999) Long-term restoration of striatal L-aromatic amino acid decarboxylase activity using recombinant adeno-associated viral vector gene transfer in a rodent model of Parkinson's disease. Neuroscience 92:185-196
103. Le Gal La Salle G, Robert JJ, Berrard S, Ridoux V, Stratford-Perricaudet LD, Perricaudet M, Mallet J (1993) An adenovirus vector for gene transfer into neurons and glia in the brain. Science 259:988-990
104. Leone P, McPhee SW, Janson CG, Davidson BL, Freese A, During MJ (2000) Multi-site partitioned delivery of human tyrosine hydroxylase gene with phenotypic recovery in parkinsonian rats. Neuroreport 11:1145-1151
105. Levivier M, Przedborski S, Bencsics C, Kang UJ (1995) Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson's disease. J Neurosci 15:7810-7820
106. Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130-1132
107. Liste I, Navarro B, Johansen J, Bueno C, Villa A, Johansen TE, Martinez-Serrano A (2004) Low-level tyrosine hydroxylase (TH) expression allows for the generation of stable TH+ cell lines of human neural stem cells. Hum Gene Ther 15:13-20
108. Ljungberg MC, Stern G, Wilkin GP (1999) Survival of genetically engineered, adult-derived rat astrocytes grafted into the 6-hydroxydopamine lesioned adult rat striatum. Brain Res 816:29-37
109. Lowenstein PR, Suwelack D, Hurtado A, Millan E, Castro MG (2003) Neuronal-specific expression of Gli-1 is neuroprotective in experimental Parkinson's disease, without an increase in efficacy when compared to a pancellular promoter. Program no. 451.1.2003 abstract viewer/itinerary planner. Society for Neuroscience, Washington DC
110. Lundberg C, Horellou P, Mallet J, Björklund A (1996) Generation of DOPA-producing astrocytes by retroviral transduction of the human tyrosine hydroxylase gene: in vitro characterization and in vivo effects in the rat Parkinson model. Exp Neurol 139:39-53
111. Luo J, Kaplitt MG, Fitzsimons HL, Zuzga DS, Liu Y, Oshinsky ML, During MJ (2002) Subthalamic GAD gene therapy in a Parkinson's disease rat model. Science 298:425-429
112. Mandel RJ, Spratt SK, Snyder RO, Leff SE (1997) Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson's disease in rats. Proc Natl Acad Sci USA 94:14083-14088
113. Mandel RJ, Rendahl KG, Spratt SK, Snyder RO, Cohen LK, Leff SE (1998) Characterization of intrastriatal recombinant adeno-associated virus-mediated gene transfer of human tyrosine hydroxylase and human GTP-cyclohydrolase I in a rat model of Parkinson's disease. J Neurosci 18:4271-4284
114. Mandel RJ, Snyder RO, Leff SE (1999) Recombinant adeno-associated viral vector-mediated glial cell line-derived neurotrophic factor gene transfer protects nigral dopamine neurons after onset of progressive degeneration in a rat model of Parkinson's disease. Exp Neurol 160:205-214
115. McGrath J, Lintz E, Hoffer BJ, Gerhardt GA, Quintero EM, Granholm AC (2002) Adeno-associated viral delivery of GDNF promotes recovery of dopaminergic phenotype following a unilateral 6-hydroxydopamine lesion. Cell Transplant 11:215-227
116. Mochizuki H, Hayakawa H, Migita M, Shibata M, Tanaka R, Suzuki A, Shimo-Nakanishi Y, Urabe T, Yamada M, Tamayose K, Shimada T, Miura M, Mizuno Y (2001) An AAV-derived Apaf-1 dominant negative inhibitor prevents MPTP toxicity as antiapoptotic gene therapy for Parkinson's disease. Proc Natl Acad Sci USA 98:10918-10923
117. Muramatsu S, Fujimoto K, Ikeguchi K, Shizuma N, Kawasaki K, Ono F, Shen Y, Wang L, Mizukami H, Kume A, Matsumura M, Nagatsu I, Urano F, Ichinose H, Nagatsu T, Terao K, Nakano I, Ozawa K (2002) Behavioral recovery in a primate model of Parkinson's disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes. Hum Gene Ther 13:345-354
118. Nakai H, Montini E, Fuess S, Storm TA, Grompe M, Kay MA (2003) AAV serotype 2 vectors preferentially integrate into active genes in mice. Nat Genet 34:297-302
119. Nakao N, Frodl EM, Widner H, Carlson E, Eggerding FA, Epstein CJ, Brundin P (1995) Overexpressing Cu/Zn superoxide dismutase enhances survival of transplanted neurons in a rat model of Parkinson's disease. Nat Med 1:226-231
120. Natsume A, Mata M, Goss J, Huang S, Wolfe D, Oligino T, Glorioso J, Fink DJ (2001) Bcl-2 and GDNF delivered by HSV-mediated gene transfer act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration. Exp Neurol 169:231-238
121. Nutt JG, Burchiel KJ, Comella CL, Jankovic J, Lang AE, Laws ER Jr, Lozano AM, Penn RD, Simpson RK Jr, Stacy M, Wooten GF, ICV GDNF Study Group (2003) Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 60:69-73
122. Oransky I (2004) Gene therapy trial for Parkinson's disease begins. Lancet 362:712
123. Ostenfeld T, Tai YT, Martin P, Deglon N, Aebischer P, Svendsen CN (2002) Neurospheres modified to produce glial cell line-derived neurotrophic factor increase the survival of transplanted dopamine neurons. J Neurosci Res 69:955-965
124. Paillard F (1999) Gene transfer to neurons with Herpes simplex virus/adeno-associated virus hybrid vectors. Hum Gene Ther 10:2441-2443
125. Palfi S, Leventhal L, Chu Y, Ma SY, Emborg M, Bakay R, Deglon N, Hantraye P, Aebischer P, Kordower JH (2002) Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration. J Neurosci 22:4942-4954
126. Palella TD, Hidaka Y, Silverman LJ, Levine M, Glorioso J, Kelley WN (1989) Expression of human HPRT mRNA in brains of mice infected with a recombinant Herpes simplex virus-1 vector. Gene 80:137-144
127. Parr MJ, Wen PY, Schaub M, Khoury SJ, Sayegh MH, Fine HA (1998) Immune parameters affecting adenoviral vector gene therapy in the brain. J Neurovirol 4:194-203
128. Peltekian E, Parrish E, Bouchard C, Peschanski M, Lisovoski F (1997) Adenovirus-mediated gene transfer to the brain: methodological assessment. J Neurosci Methods 71:77-84
129. Robbins PD, Tahara H, Ghivizzani SC (1998) Viral vectors for gene therapy. Trends Biotechnol 16:35-40
130. Robert JJ, Bouilleret V, Ridoux V, Valin A, Geoffroy MC, Mallet J, Le Gal La Salle G (1997) Adenovirus-mediated transfer of a functional GAD gene into nerve cells: potential for the treatment of neurological diseases. Gene Ther 4:1237-1245
131. Robertson GS, Banner D, Cregan SP, Smith PD, Mount MP, Marcelissen RS, Liston P, Crocker SJ, Park DS (2003) The RING finger domain of XIAP prevents 6-hydroxydopamine-induced dopamine neuron death. Program no. 410.18.2003 abstract viewer/itinerary planner. Society for Neuroscience, Washington DC
132. Rosenblad C, Georgievska B, Kirik D (2003) Long-term striatal overexpression of GDNF selectively downregulates tyrosine hydroxylase in the intact nigrostriatal dopamine system. Eur J Neurosci 17:260-270
133. Rosenblad C, Gronborg M, Hansen C, Blom N, Meyer M, Johansen J, Dago L, Kirik D, Patel UA, Lundberg C, Trono D, Björklund A, Johansen TE (2000) In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin. Mol Cell Neurosci 15:199-214 (Erratum, 2001, 18:332-333)
134. Sabate O, Horellou P, Vigne E, Colin P, Perricaudet M, Buc-Caron MH, Mallet J (1995) Transplantation to the rat brain of human neural progenitors that were genetically modified using adenoviruses. Nat Genet 9:256-260
135. Sautter J, Tseng JL, Braguglia D, Aebischer P, Spenger C, Seiler RW, Widmer HR, Zurn AD (1998) Implants of polymer-encapsulated genetically modified cells releasing glial cell line-derived neurotrophic factor improve survival, growth, and function of fetal dopaminergic grafts. Exp Neurol 149:230-236
136. Schlachetzki F, Zhang Y, Boado RJ, Pardridge WM (2004) Gene therapy of the brain: the trans-vascular approach. Neurology 62:1275-1281
137. Schneider JS, Wade TV (2003) Experimental parkinsonism is associated with increased pallidal GAD gene expression and is reversed by site-directed antisense gene therapy. Mov Disord 18:32-40
138. Schwaiting RK, Huston JP (1996a) Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their physiological sequelae. Prog Neurobiol 49:215-266
139. Schwarting RK, Huston JP (1996b) The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments. Prog Neurobiol 50:275-331
140. Schwarz EJ, Alexander GM, Prockop DJ, Azizi SA (1999) Multipotential marrow stromal cells transduced to produce L-DOPA: engraftment in a rat model of Parkinson disease. Hum Gene Ther 10:2539-2549
141. Segovia J, Vergara P, Brenner M (1998) Astrocyte-specific expression of tyrosine hydroxylase after intracerebral gene transfer induces behavioral recovery in experimental parkinsonism. Gene Ther 5:1650-1655
142. Shen Y, Muramatsu SI, Ikeguchi K, Fujimoto KI, Fan DS, Ogawa M, Mizukami H, Urabe M, Kume A, Nagatsu I, Urano F, Suzuki T, Ichinose H, Nagatsu T, Monahan J, Nakano I, Ozawa K (2000) Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic-L-amino-acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson's disease. Hum Gene Ther 11:1509-1519
143. Shi N, Zhang Y, Zhu C, Boado RJ, Pardridge WM (2001) Brain-specific expression of an exogenous gene after i.v. administration. Proc Natl Acad Sci USA 98:12754-12759
144. Shim JW, Koh HC, Chang MY, Roh E, Choi CY, Oh YJ, Son H, Lee YS, Studer L, Lee SH (2004) Enhanced in vitro midbrain dopamine neuron differentiation, dopaminergic function, neurite outgrowth, and 1-methyl-4-phenylpyridium resistance in mouse embryonic stem cells overexpressing Bcl-XL. J Neurosci 24:843-852
145. Shingo T, Date I, Yoshida H, Ohmoto T (2002) Neuroprotective and restorative effects of intrastriatal grafting of encapsulated GDNF-producing cells in a rat model of Parkinson's disease. J Neurosci Res 69:946-954
146. Shisler JL, Gooding LR (1998) Adenoviral inhibitors of the apoptotic cascade. Trends Microbiol 6:337-339
147. Smith PD, Crocker SJ, Jackson-Lewis V, Jordan-Sciutto KL, Hayley S, Mount MP, O'Hare MJ, Callaghan S, Slack RS, Przedborski S, Anisman H, Park DS (2003) Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease. Proc Natl Acad Sci USA 100:13650-13655
148. Stilwell JL, Samulski RJ (2003) Adeno-associated virus vectors for therapeutic gene transfer. Biotechniques 34:148-154
149. Studer L, Tabar V, McKay RD (1998) Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nat Neurosci 1:290-295
150. Sun M, Kong L, Wang X, Holmes C, Zhang G, Goldstein DS, Geller AI (2003) Coexpression of four dopamine biosynthetic and release genes (TH, GTP CH, AADC, VMAT) from a HSV-1 vector supports efficient biochemical and behavioral correction of a rat model of Parkinson's disease. 2003 Abstract viewer/itinerary planner. Society for Neuroscience, Washington DC
151. Sun M, Zhang GR, Kong L, Holmes C, Wang X, Zhang W, Goldstein DS, Geller AI (2003b) Correction of a rat model of Parkinson's disease by coexpression of tyrosine hydroxylase and aromatic amino acid decarboxylase from a helper virus-free Herpes simplex virus type 1 vector. Hum Gene Ther 14:415-424
152. Takayama H, Ray J, Raymon HK, Baird A, Hogg J, Fisher LJ, Gage FH (1995) Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson's disease. Nat Med 1:53-58
153. Thomas CE, Schiedner G, Kochanek S, Castro MG, Lowenstein PR (2000) 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 USA 97:7482-7487
154. Tomac A, Lindqvist E, Lin LF, Ogren SO, Young D, Hoffer BJ, Olson L (1995) Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373:335-339
155. Trejo F, Vergara P, Brenner M, Segovia J (1999) Gene therapy in a rodent model of Parkinson's disease using differentiated C6 cells expressing a GFAP-tyrosine hydroxylase transgene. Life Sci 65:483-491
156. Tripathy SK, Black HB, Goldwasser E, Leiden JM (1996) Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat Med 2:545-550
157. Umegaki H, Chernak JM, Ikari H, Roth GS, Ingram DK (1997) Rotational behavior produced by adenovirus-mediated gene transfer of dopamine D2 receptor into rat striatum. Neuroreport 10:3553-3558
158. Viswanath V, Wu Y, Boonplueang R, Chen S, Stevenson FF, Yantiri F, Yang L, Beal MF, Andersen JK (2001) Caspase-9 activation results in downstream caspase-8 activation and bid cleavage in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced Parkinson's disease. J Neurosci 21:9519-9528
159. Vogel R, Amar L, Thi AD, Saillour P, Mallet J (2004) A single lentivirus vector mediates doxycycline-regulated expression of transgenes in the brain. Hum Gene Ther 15:157-165
160. Wachtel SR, Bencsics C, Kang UJ (1997) Role of aromatic L-amino acid decarboxylase for dopamine replacement by genetically modified fibroblasts in a rat model of Parkinson's disease. J Neurochem 69:2055-2063
161. Wahlestedt C, Golanov E, Yamamoto S, Yee F, Ericson H, Yoo H, Inturrisi CE, Reis DJ (1993) Antisense oligodeoxynucleotides to NMDA-R1 receptor channel protect cortical neurons from excitotoxicity and reduce focal ischaemic infarctions. Nature 363:260-263
162. Wang L, Muramatsu S, Lu Y, Ikeguchi K, Fujimoto K, Okada T, Mizukami H, Hanazono Y, Kume A, Urano F, Ichinose H, Nagatsu T, Nakano I, Ozawa K (2002a) Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease. Gene Ther 9:381-389
163. Wang ZH, Ji Y, Shan W, Zeng B, Raksadawan N, Pastores GM, Wisniewski T, Kolodny EH (2002b) Therapeutic effects of astrocytes expressing both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model of Parkinson's disease. Neuroscience 113:629-640
164. Widenfalk J, Nosrat C, Tomac A, Westphal H, Hoffer B, Olson L (1997) Neurturin and glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta), novel proteins related to GDNF and GDNFR-alpha with specific cellular patterns of expression suggesting roles in the developing and adult nervous system and in peripheral organs. J Neurosci 17:8506-8519
165. Wolff JA, Fisher LJ, Xu L, Jinnah HA, Langlais PJ, Iuvone PM, O'Malley KL, Rosenberg MB, Shimohama S, Friedmann T, et al (1989) Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease. Proc Natl Acad Sci USA 86:9011-9014
166. Wyman T, Rohrer D, Kirigiti P, Nichols H, Pilcher K, Nilaver G, Machida C (1999) Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases. Gene Ther 6:1648-1660
167. Xia XG, Harding T, Weller M, Bieneman A, Uney JB, Schulz JB (2001) Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease. Proc Natl Acad Sci USA 98:10433-10438
168. Xu R, Liu J, Chen X, Xu F, Xie Q, Yu H, Guo Q, Zhou X, Jin Y (2001) Ribozyme-mediated inhibition of caspase-3 activity reduces apoptosis induced by 6-hydroxydopamine in PC12 cells. Brain Res 899:10-19
169. Yamada M, Oligino T, Mata M, Goss JR, Glorioso JC, Fink DJ (1999) Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine- induced degeneration of neurons in the substantia nigra in vivo. Proc Natl Acad Sci USA 96:4078-4083
170. Yamada H, Dezawa M, Shimazu S, Baba M, Sawada H, Kuroiwa Y, Yamamoto I, Kanno H (2003) Transfer of the von Hippel-Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease. Ann Neurol 54:352-359
171. Yang Y, Kaul S, Zhang D, Anantharam V, Kanthasamy AG (2004) Suppression of caspase-3-dependent proteolytic activation of protein kinase Cdelta by small interfering RNA prevents MPP +-induced dopaminergic degeneration. Mol Cell Neurosci 25:406-421
172. Yoshimoto Y, Lin Q, Collier TJ, Frim DM, Breakefield XO, Bohn MC (1995) Astrocytes retrovirally transduced with BDNF elicit behavioral improvement in a rat model of Parkinson's disease. Brain Res 691:25-36
173. Zhang Z, Miyoshi Y, Lapchak PA, Collins F, Hilt D, Lebel C, Kryscio R, Gash DM (1997) Dose response to intraventricular glial cell line-derived neurotrophic factor administration in parkinsonian monkeys. J Pharmacol Exp Ther 282:1396-1401
174. Zhang Y, Calon F, Zhu C, Boado RJ, Pardridge WM (2003) Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism. Hum Gene Ther 14:1-12
175. Zhang Y, Schlachetzki F, Zhang YF, Boado RJ, Pardridge WM (2004) Normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism with intravenous nonviral gene therapy and a brain-specific promoter. Hum Gene Ther 15:339-350
176. Zurn AD, Widmer HR, Aebischer P (2001) Sustained delivery of GDNF: towards a treatment for Parkinson's disease. Brain Res Brain Res Rev 36:222-229