Parkinson's disease: Gene therapies

Cold Spring Harbor Perspectives in Medicine

Volumn 2, Issue 4, 2012, Pages

  Coune, Philippe G ^a   Schneider, Bernard L ^a   Aebischer, Patrick ^a  

^a EPFL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; ANTIPARKINSON AGENT; FLUORODEOXYGLUCOSE F 18; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GLUTAMATE DECARBOXYLASE 65; GLUTAMATE DECARBOXYLASE 67; LENTIVIRUS VECTOR; LEVODOPA; NEURTURIN; PARKIN; PARVOVIRUS VECTOR; PROSAVIN; RACLOPRIDE C 11; UNCLASSIFIED DRUG; VESICULAR MONOAMINE TRANSPORTER 2; GLUTAMATE DECARBOXYLASE; UBIQUITIN PROTEIN LIGASE;

CENTRAL NERVOUS SYSTEM; DOPAMINE METABOLISM; ENZYME REPLACEMENT; GENE EXPRESSION; HUMAN; MPTP-INDUCED PARKINSONISM; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PHASE 2 CLINICAL TRIAL (TOPIC); REVIEW; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; ADENO ASSOCIATED VIRUS; GENE THERAPY; GENE VECTOR; GENETICS; LENTIVIRINAE; METABOLISM;

ALPHA-SYNUCLEIN; DEPENDOVIRUS; GENETIC THERAPY; GENETIC VECTORS; GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR; GLUTAMATE DECARBOXYLASE; HUMANS; LENTIVIRUS; LEVODOPA; PARKINSON DISEASE; UBIQUITIN-PROTEIN LIGASES;

EID: 84877055074     PISSN: None     EISSN: 21571422     Source Type: Journal    
DOI: 10.1101/cshperspect.a009431     Document Type: Review

References (100)

1. Ai Y, Markesbery W, Zhang Z, Grondin R, Elseberry D, Gerhardt GA, Gash DM. 2003. Intraputamenal infusion of GDNF in aged rhesus monkeys: Distribution and dopaminergic effects. J Comp Neurol 461: 250-261.
2. 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.
3. 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. J Neurosci 22: 10302-10312.
4. 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.
5. Bankiewicz KS, Forsayeth J, Eberling JL, Sanchez-Pernaute R, Pivirotto P, Bringas J, Herscovitch P, Carson RE, Eckelman W, Reutter B, et al. 2006. Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol Ther 14: 564-570.
6. Bartus RT, Herzog CD, Chu Y, Wilson A, Brown L, Siffert J, Johnson EM, OlanowCW, Mufson EJ, Kordower JH. 2011. Bioactivity of AAV2-neurturin gene therapy (CERE-120): Differences between Parkinson's disease and nonhuman primate brains. Movement Disorders 26: 27-36.
7. Beck KD, Valverde J, Alexi T, Poulsen K, Moffat B, Vandlen RA, Rosenthal A, Hefti F. 1995. Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain. Nature 373: 339-341.
8. Björklund T, Carlsson T, Cederfjäll EA, Carta M, Kirik D. 2010. Optimized adeno-associated viral vector-mediated striatal DOPA delivery restores sensorimotor function and prevents dyskinesias in a model of advanced Parkinson's disease. Brain 133: 496-511.
9. Büning H, Perabo L, Coutelle O, Quadt-Humme S, Hallek M. 2008. Recent developments in adeno-associated virus vector technology. J Gene Med 10: 717-733.
10. Carlsson T, Winkler C, Burger C, Muzyczka N, Mandel RJ, Cenci A, Björklund A, Kirik D. 2005. Reversal of dyskinesias in an animal model of Parkinson's disease by continuous L-DOPA delivery using rAAV vectors. Brain 128: 559-569.
11. Chen L, Ding Y, Cagniard B, Van Laar AD, Mortimer A, Chi W, Hastings TG, Kang UJ, Zhuang X. 2008. Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative stress in mice. J Neurosci 28: 425-433.
12. Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, VanBrocklin HF, Wright JF, Bankiewicz KS, Aminoff MJ. 2009. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 73: 1662-1669.
13. Cotzias GC, Papavasiliou PS, Gellene R. 1969. Modification of Parkinsonism-chronic treatment with L-dopa. N Engl J Med 280: 337-345.
14. 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.
15. Cyr M, Beaulieu J-M, Laakso A, Sotnikova TD, Yao W-D, Bohn LM, GainetdinovRR, Caron MG. 2003. Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons. Proc Natl Acad Sci 100: 11035-11040.
16. Decressac M, Ulusoy A, Mattsson B, Georgievska B, Romero-Ramos M, Kirik D, Björklund A. 2011. GDNF fails to exert neuroprotection in a rat {α}-synuclein model of Parkinson's disease. Brain 134: 2302-2311.
17. Deierborg T, Soulet D, Roybon L, Hall V, Brundin P. 2008. Emerging restorative treatments for Parkinson's disease. Progress Neurobiol 85: 407-432.
18. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L. 1998. A third-generation lentivirus vector with a conditional packaging system. J Virol 72: 8463-8471.
19. Eberling JL, Jagust WJ, Christine CW, Starr P, Larson P, Bankiewicz KS, AminoffMJ. 2008. Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology 70: 1980-1983.
20. Emborg ME, Carbon M, Holden JE, During MJ, Ma Y, Tang C, Moirano J, Fitzsimons H, Roitberg BZ, Tuccar E, et al. 2007. Subthalamic glutamic acid decarboxylase gene therapy: Changes in motor function and cortical metabolism. J Cerebral Blood Flow Metabol 27: 501-509.
21. Feigin A, Kaplitt MG, Tang C, Lin T, Mattis P, Dhawan V, During MJ, EidelbergD. 2007. Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease. Proc Natl Acad Sci 104: 19559-19564.
22. +toxicity and reduces dopamine transport. J Neurosci Res 85: 351-363.
23. Gasmi M, Brandon EP, Herzog CD, Wilson A, Bishop KM, Hofer EK, CunninghamJJ, Printz MA, Kordower JH, Bartus RT. 2007a. AAV2-mediated delivery of human neurturin to the rat nigrostriatal system: Long-term efficacy and tolerability of CERE-120 for Parkinson's disease. Neurobiol Dis 27: 67-76.
24. Gasmi M, Herzog CD, Brandon EP, Cunningham JJ, Ramirez GA, Ketchum ET, Bartus RT. 2007b. Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neuron degeneration in Parkinson's disease. Mol Ther 15: 62-68.
25. 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.
26. Gorbatyuk OS, Li S, Nash K, Gorbatyuk M, Lewin AS, Sullivan LF, Mandel RJ, Chen W, Meyers C, Manfredsson FP, et al. 2010. In vivo RNAi-mediated α-synuclein silencing induces nigrostriatal degeneration. Mol Ther 18: 1450-1457.
27. Grimm D, Kay MA, Kleinschmidt JA. 2003. Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6. Mol Ther 7: 839-850.
28. Grondin R, Zhang Z, Yi A, Cass WA, Maswood N, Andersen AH, Elsberry DD, Klein MC, Gerhardt GA, Gash DM. 2002. Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys. Brain 125: 2191-2201.
29. Grondin R, Cass WA, Zhang Z, Stanford JA, Gash DM, Gerhardt GA. 2003. Glial cell line-derived neurotrophic factor increases stimulus-evoked dopamine release and motor speed in aged rhesus monkeys. J Neurosci 23: 1974-1980.
30. Hayashita-Kinoh H, Yamada M, Yokota T, Mizuno Y, Mochizuki H. 2006. Down-regulation of α-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson's disease rat model. Biochem Biophys Res Commun 341: 1088-1095.
31. Hoane MR, Gulwadi AG, Morrison S, Hovanesian G, Lindner MD, Tao W. 1999. Differential in vivo effects of neurturin and glial cell-line-derived neurotrophic factor. Exp Neurol 160: 235-243.
32. Huser D, Gogol-Doring A, Lutter T, Weger S, Winter K, Hammer EM, CathomenT, Reinert K, Heilbronn R. 2010. Integration preferences of wildtype AAV-2 for consensus rep-binding sites at numerous loci in the human genome. PLoS Pathogens 6: e1000985.
33. Hyun D-H, Lee M, Hattori N, Kubo S-I, Mizuno Y, Halliwell B, Jenner P. 2002. Effect of wild-type or mutant Parkin on oxidative damage, nitric oxide, antioxidant defenses, and the proteasome. J Biol Chem 277: 28572-28577.
34. Ichinose H, Ohye T, Fujita K, Pantucek F, Lange K, Riederer P, Nagatsu T. 1994. Quantification of mRNA of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the substantia nigra in Parkinson's disease and schizophrenia. J Neural Transm Park Dis Dement Sect 8: 149-158.
35. Jarraya B, Boulet S, Ralph GS, Jan C, Bonvento G, Azzouz M, Miskin JE, Shin M, Delzescaux T, Drouot X, et al. 2009. Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia. Sci Transl Med 1: 2ra4.
36. Johnston LC, Eberling J, Pivirotto P, Hadaczek P, Federoff HJ, Forsayeth J, Bankiewicz KS. 2009. Clinically relevant effects of convection-enhanced delivery of AAV2-GDNF on the dopaminergic nigrostriatal pathway in aged rhesus monkeys. Hum Gene Ther 20: 497-510.
37. Junn E, Lee K-W, Jeong BS, Chan TW, Im J-Y, Mouradian MM. 2009. Repression of α-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci 106: 13052-13057.
38. Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, et al. 2007. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: An open label, phase I trial. Lancet 369: 2097-2105.
39. Kearns CM, Gash DM. 1995. GDNF protects nigral dopamine neurons against 6-hydroxydopamine in vivo. Brain Res 672: 104-111.
40. Kettler R, Bartholini G, Pletscher A. 1974. In vivo enhancement of tyrosine hydroxylation in rat striatum by tetrahydrobiopterin. Nature 249: 476-478.
41. Khan NL, Brooks DJ, Pavese N, Sweeney MG, Wood NW, Lees AJ, Piccini P. 2002. Progression of nigrostriatal dysfunction in a parkin kindred: An [18F]dopa PET and clinical study. Brain 125: 2248-2256.
42. Kirik D, Rosenblad C, Björklund A. 2000. Preservation of a functional nigrostriatal dopamine pathway by GDNF in the intrastriatal 6-OHDA lesion model depends on the site of administration of the trophic factor. Eur J Neurosci 12: 3871-3882.
43. Kirik D, Georgievska B, Burger C, Winkler C, Muzyczka N, Mandel RJ, BjorklundA. 2002. Reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of L-dopa using rAAV-mediated gene transfer. Proc Natl Acad Sci 99: 4708-4713.
44. Kish SJ, Tong J, Hornykiewicz O, Rajput A, Chang L-J, Guttman M, Furukawa Y. 2008. Preferential loss of serotonin markers in caudate versus putamen in Parkinson's disease. Brain 131: 120-131.
45. Kishima H, Poyot T, Bloch J, Dauguet J, Condé F, Dollé F, Hinnen F, Pralong W, Palfi S, Déglon N, et al. 2004. Encapsulated GDNF-producing C2C12 cells for Parkinson's disease: A pre-clinical study in chronic MPTP-treated baboons. Neurobiol Dis 16: 428-439.
46. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. 1998. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392: 605-608.
47. Kordower JH, Palfi S, Chen EY, Ma SY, Sendera T, Cochran EJ, Mufson EJ, PennR, Goetz CG, Comella CD. 1999. Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease. Ann Neurol 46: 419-424.
48. Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, ChenEY, Palfi S, Roitberg BZ, et al. 2000. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 290: 767-773.
49. Kordower JH, Herzog CD, Dass B, Bakay RAE, Stansell J, Gasmi M, Bartus RT. 2006. Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. Ann Neurol 60: 706-715.
50. Kumar M, Keller B, Makalou N, Sutton RE. 2001. Systematic determination of the packaging limit of lentiviral vectors. Hum Gene Ther 12: 1893-1905.
51. Kwon I, Schaffer DV. 2008. Designer gene delivery vectors: Molecular engineering and evolution of adeno-associated viral vectors for enhanced gene transfer. Pharmaceut Res 25: 489-499.
52. Lee B, Lee H, Nam YR, Oh JH, Cho YH, Chang JW. 2005. Enhanced expression of glutamate decarboxylase 65 improves symptoms of rat parkinsonian models. Gene Therapy 12: 1215-1222.
53. Leriche L, Björklund T, Breysse N, Besret L, Grégoire M-C, Carlsson T, Dollé F, Mandel RJ, Déglon N, Hantraye P, et al. 2009. Positron emission tomography imaging demonstrates correlation between behavioral recovery and correction of dopamine neurotransmission after gene therapy. J Neurosci 29: 1544-1553.
54. LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Thomas K, Sarkar A, Siddiqui MS. 2011. AAV2-GAD gene therapy for advanced Parkinson's disease: A double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 10: 309-319.
55. Lim ST, Airavaara M, Harvey BK. 2010. Viral vectors for neurotrophic factor delivery: A gene therapy approach for neurodegenerative diseases of the CNS. Pharmacol Res 61: 14-26.
56. 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.
57. Lo Bianco C, Déglon N, Pralong W, Aebischer P. 2004a. Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease. Neurobiol Dis 17: 283-289.
58. Lo Bianco C, Schneider BL, Bauer M, Sajadi A, Brice A, Iwatsubo T, Aebischer P. 2004b. Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an α-synuclein rat model of Parkinson's disease. Proc Natl Acad Sci 101: 17510-17515.
59. 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.
60. Maersch S, Huber A, Büning H, Hallek M, Perabo L. 2010. Optimization of stealth adeno-associated virus vectors by randomization of immunogenic epitopes. Virology 397: 167-175.
61. Manfredsson FP, Burger C, Sullivan LF, Muzyczka N, Lewin AS, Mandel RJ. 2007. rAAV-mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of Parkinson's disease. Exp Neurol 207: 289-301.
62. Maraganore DM, de Andrade M, Elbaz A, Farrer MJ, Ioannidis JP, Krüger R, Rocca WA, Schneider NK, Lesnick TG, Lincoln SJ, et al. 2006. Collaborative analysis of α-synuclein gene promoter variability and Parkinson disease. JAMA296: 661-670.
63. Marks WJ Jr., Ostrem JL, Verhagen L, Starr PA, Larson PS, Bakay RA, Taylor R, Cahn-Weiner DA, Stoessl AJ, Olanow CW. 2008. Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson's disease: An open-label, phase I trial. Lancet Neurol 7: 400-408.
64. Marks WJ Jr., Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, Vitek J, Stacy M, Turner D, Verhagen L. 2010. Gene delivery of AAV2-neurturin for Parkinson's disease: A double-blind, randomised, controlled trial. Lancet Neurol 9: 1164-1172.
65. McCormack AL, Mak SK, Henderson JM, Bumcrot D, Farrer MJ, Di Monte DA. 2010. α-synuclein suppression by targeted small interfering RNA in the primate substantia nigra. PloS ONE 5: e12122.
66. Moffat M, Harmon S, Haycock J, O'Malley KL. 1997. L-Dopa and dopamine-producing gene cassettes for gene therapy approaches to Parkinson's disease. Exp Neurol 144: 69-73.
67. Montini E, Cesana D, Schmidt M, Sanvito F, Ponzoni M, Bartholomae C, Sergi Sergi L, Benedicenti F, Ambrosi A, Di Serio C, et al. 2006. Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol 24: 687-696.
68. Moskalenko M, Chen L, van Roey M, Donahue BA, Snyder RO, McArthur JG, Patel SD. 2000. Epitope mapping of human anti-adeno-associated virus Type 2 neutralizing antibodies: Implications for gene therapy and virus structure. J Virol 74: 1761-1766.
69. Muramatsu S-I, Fujimoto K-I, Ikeguchi K, Shizuma N, Kawasaki K, Ono F, ShenY, Wang L, Mizukami H, Kume A, et al. 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.
70. Naldini L, Blömer U, Gage FH, Trono D, Verma IM. 1996a. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci 93: 11382-11388.
71. Naldini L, Blömer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D. 1996b. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272: 263-267.
72. Narendra D, Tanaka A, Suen D-F, Youle RJ. 2008. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183: 795-803.
73. Nishioka K, Hayashi S, Farrer MJ, Singleton AB, Yoshino H, Imai H, Kitami T, Sato K, Kuroda R, Tomiyama H, et al. 2006. Clinical heterogeneity of α-synuclein gene duplication in Parkinson's disease. Ann Neurol 59: 298-309.
74. Nutt JG, Burchiel KJ, Comella CL, Jankovic J, Lang AE, Laws ER, Lozano AM, Penn RD, Simpson RK, Stacy M, et al. 2003. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 60: 69-73.
75. Olsen JC. 1998. Gene transfer vectors derived from equine infectious anemia virus. Gene Therapy 5: 1481-1487.
76. Palfi S, Leventhal L, Chu Y, Ma SY, Emborg M, Bakay R, Déglon 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.
77. Park K. 2001. Protection of nigral neurons by GDNF-engineered marrow cell transplantation. Neurosci Res 40: 315-323.
78. Pascual A, Hidalgo-Figueroa M, Piruat JI, Pintado CO, Gómez-Díaz R, López-Barneo J. 2008. Absolute requirement of GDNF for adult catecholaminergic neuron survival. Nat Neurosci 11: 755-761.
79. Paterna J-C, Feldon J, Büeler H. 2004. Transduction profiles of recombinant adeno-associated virus vectors derived from serotypes 2 and 5 in the nigrostriatal system of rats. J Virol 78: 6808-6817.
80. Paterna J-C, Leng A, Weber E, Feldon J, Büeler H. 2007. DJ-1 and Parkin modulate dopamine-dependent behavior and inhibit MPTP-induced nigral dopamine neuron loss in mice. Mol Ther 15: 698-704.
81. Rahim AA, Wong AMS, Howe SJ, Buckley SMK, Acosta-Saltos AD, Elston KE, Ward NJ, Philpott NJ, Cooper JD, Anderson PN, et al. 2009. Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors. Gene Therapy 16: 509-520.
82. Rosenblad C, Kirik D, Devaux B, Moffat B, Phillips HS, Björklund A. 1999. Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle. Eur J Neurosci 11: 1554-1566.
83. Sajadi A, Bensadoun J-C, Schneider BL, Lo Bianco C, Aebischer P. 2006. Transient striatal delivery of GDNF via encapsulated cells leads to sustained behavioral improvement in a bilateral model of Parkinson disease. Neurobiol Disease 22: 119-129.
84. Samulski RJ, Chang LS, Shenk T. 1989. Helper-free stocks of recombinant adeno-associated viruses: Normal integration does not require viral gene expression. J Virol 63: 3822-3828.
85. Samulski RJ, Zhu X, Xiao X, Brook JD, Housman DE, Epstein N, Hunter LA. 1991. Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J 10: 3941-3950.
86. Sapru MK, Yates JW, Hogan S, Jiang L, Halter J, Bohn MC. 2006. Silencing of human α-synuclein in vitro and in rat brain using lentiviral-mediated RNAi. Exp Neurol 198: 382-390.
87. Sauer H, Rosenblad C, Björklund A. 1995. Glial cell line-derived neurotrophic factor but not transforming growth factor β 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion. Proc Natl Acad Sci 92: 8935-8939.
88. Shen Y, Muramatsu SI, Ikeguchi K, Fujimoto KI, Fan DS, Ogawa M, Mizukami H, Urabe M, Kume A, Nagatsu I, et al. 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.
89. Shimura H, Hattori N, Kubo Si, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, et al. 2000. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Gen 25: 302-305.
90. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, HulihanM, Peuralinna T, Dutra A, Nussbaum R, et al. 2003. α-Synuclein locus triplication causes Parkinson's disease. Science 302: 841.
91. Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, et al. 2009. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136: 964-977.
92. Soldner F, Laganière J, Cheng AW, Hockemeyer D, Gao Q, Alagappan R, Khurana V, Golbe LI, Myers RH, Lindquist S, et al. 2011. Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146: 318-331.
93. Sun M, Zhang G-R, Kong L, Holmes C, Wang X, Zhang W, Goldstein DS, GellerAI. 2003. 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.
94. Tseng JL, Baetge EE, Zurn AD, Aebischer P. 1997. GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine. J Neurosci 17: 325-333.
95. Vercammen L, Van der Perren A, Vaudano E, Gijsbers R, Debyser Z, Van den Haute C, Baekelandt V. 2006. Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's disease. Mol Ther 14: 716-723.
96. Yamada M, Mizuno Y, Mochizuki H. 2005. Parkin gene therapy for α-synucleinopathy: A rat model of Parkinson's disease. Hum Gene Ther 16: 262-270.
97. Yang Y, Nishimura I, Imai Y, Takahashi R, Lu B. 2003. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron 37: 911-924.
98. Yasuda T, Miyachi S, Kitagawa R, Wada K, Nihira T, Ren Y-R, Hirai Y, AgeyamaN, Terao K, Shimada T, et al. 2007. Neuronal specificity of α-synuclein toxicity and effect of Parkin co-expression in primates. Neuroscience 144: 743-753.
99. Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D. 1997. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 15: 871-875.
100. Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L, Trono D. 1998. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 72: 9873-9880.