Development of advanced therapies based on viral vector-mediated overexpression of therapeutic molecules and knockdown of disease-related genes for Parkinson's disease

Therapeutic Delivery

Volumn 2, Issue 1, 2011, Pages 37-50

  Ulusoy, Ayse ^a,b   Kirik, Deniz ^a  

^a LUND UNIVERSITY   (Sweden)

^b GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC LEVO AMINO ACID DECARBOXYLASE; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE I; LENTIVIRUS VECTOR; LEVODOPA; NEUROTROPHIC FACTOR; NEURTURIN; PARKIN; PARVOVIRUS VECTOR; TYROSINE 3 MONOOXYGENASE;

CONTINUOUS INFUSION; DISEASE COURSE; DOSE RESPONSE; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TARGETING; GENE OVEREXPRESSION; GENE SILENCING; GENE TARGETING; HUMAN; LOSS OF FUNCTION MUTATION; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; RNA INTERFERENCE; TRANSGENE; VIRAL GENE DELIVERY SYSTEM;

EID: 79954510578     PISSN: 20415990     EISSN: 20416008     Source Type: Journal    
DOI: 10.4155/tde.10.95     Document Type: Review

References (165)

1. Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 114(Pt 5), 2283-2301 (1991).
2. Birkmayer W, Hornykiewicz O. The l-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia. Wien. Klin. Wochenschr. 73, 787-788 (1961).
3. Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov. Disord. 16, 448-458 (2001). (Pubitemid 36041148)
4. Obeso JA, Olanow CW, Nutt JG. Levodopa motor complications in Parkinson's disease. Trends Neurosci. 23, S2-S7 (2000).
5. Chase TN. Levodopa therapy: consequences of the nonphysiologic replacement of dopamine. Neurology 50, S17-S25 (1998). (Pubitemid 28223748)
6. Kruger R, Kuhn W, Muller T, et al. Ala30Pro mutation in the gene encoding a-synuclein in Parkinson's disease. Nat. Genet. 18, 106-108 (1998).
7. Spillantini MG, Schmidt ML, Lee VM, et al. a-synuclein in Lewy bodies. Nature 388, 839-840 (1997).
8. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the a-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047 (1997). (Pubitemid 27443610)
9. Zarranz JJ, Alegre J, Gomez-Esteban JC, et al. The new mutation, E46K, of a-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55, 164-173 (2004). (Pubitemid 38166992)
10. Singleton AB, Farrer M, Johnson J, et al. a-synuclein locus triplication causes Parkinson's disease. Science 302, 841 (2003). (Pubitemid 37339619)
11. Chartier-Harlin MC, Kachergus J, Roumier C, et al. a-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364, 1167-1169 (2004). (Pubitemid 39296604)
12. Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608 (1998). (Pubitemid 28207717)
13. Bonifati V, Rizzu P, Squitieri F, et al. DJ-1(PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol. Sci. 24, 159-160 (2003). (Pubitemid 37304291)
14. Valente EM, Salvi S, Ialongo T, et al. PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann. Neurol. 56, 336-341 (2004). (Pubitemid 39166552)
15. Paisan-Ruiz C, Jain S, Evans EW, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595-600 (2004). (Pubitemid 39531224)
16. Zimprich A, Muller-Myhsok B, Farrer M, et al. The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval. Am. J. Hum. Genet. 74, 11-19 (2004). (Pubitemid 38085234)
17. Doss-Pepe EW, Chen L, Madura K. a-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains. J. Biol. Chem. 280, 16619-16624 (2005). (Pubitemid 41389118)
18. Gautier CA, Kitada T, Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc. Natl Acad. Sci. USA 105, 11364-11369 (2008).
19. Clements CM, McNally RS, Conti BJ, Mak TW, Ting JP. DJ-1, a cancer-and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc. Natl Acad. Sci. USA 103, 15091-15096 (2006). (Pubitemid 44583169)
20. Lu YW, Tan EK. Molecular biology changes associated with LRRK2 mutations in Parkinson's disease. J. Neurosci. Res. 86, 1895-1901 (2008).
21. Ulusoy A, Bjorklund T, Hermening S, Kirik D. In vivo gene delivery for development of mammalian models for Parkinson's disease. Exp. Neurol. 209, 89-100 (2008).
22. Grimm D. Production methods for gene transfer vectors based on adeno-associated virus serotypes. Methods 28, 146-157 (2002). (Pubitemid 35341078)
23. Zolotukhin S, Potter M, Zolotukhin I, et al. Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors. Methods 28, 158-167 (2002). (Pubitemid 35341079)
24. Geller AI, Breakefield XO. A defective HSV-1 vector expresses Escherichia coli b-galactosidase in cultured peripheral neurons. Science 241, 1667-1669 (1988).
25. Dobson AT, Margolis TP, Sedarati F, Stevens JG, Feldman LT. A latent, nonpathogenic HSV-1-derived vector stably expresses b-galactosidase in mouse neurons. Neuron 5, 353-360 (1990). (Pubitemid 20294985)
26. Geller AI, Freese A. Infection of cultured central nervous system neurons with a defective herpes simplex virus 1 vector results in stable expression of Escherichia coli beta-galactosidase. Proc. Natl Acad. Sci. USA 87, 1149-1153 (1990).
27. Le Gal La Salle G, Robert JJ, Berrard S, et al. An adenovirus vector for gene transfer into neurons and glia in the brain. Science 259, 988-990 (1993). (Pubitemid 23080671)
28. Akli S, Caillaud C, Vigne E, et al. Transfer of a foreign gene into the brain using adenovirus vectors. Nat. Genet. 3, 224-228 (1993). (Pubitemid 23096557)
29. Davidson BL, Allen ED, Kozarsky KF, Wilson JM, Roessler BJ. A model system for in vivo gene transfer into the central nervous system using an adenoviral vector. Nat. Genet. 3, 219-223 (1993). (Pubitemid 23096556)
30. 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. 3, 229-234 (1993). (Pubitemid 23096558)
31. Kaplitt MG, Leone P, Samulski RJ, et al. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat. Genet. 8, 148-154 (1994). (Pubitemid 24308362)
32. Mandel RJ, Rendahl KG, Spratt SK, et al. 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 (1998). (Pubitemid 28243820)
33. Bencsics C, Wachtel SR, Milstien S, et al. 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 (1996). (Pubitemid 26243040)
34. Fitzpatrick PF. Mechanistic studies of tyrosine hydroxylase. Adv. Exp. Med. Biol. 338, 81-86 (1993). (Pubitemid 23340552)
35. Fitzpatrick PF. Studies of the rate-limiting step in the tyrosine hydroxylase reaction: alternate substrates, solvent isotope effects, and transition-state analogues. Biochemistry 30, 6386-6391 (1991).
36. Fukushima K, Richter WE Jr, Shiota T. Partial purification of 6-(d-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropterin triphosphate synthetase from chicken liver. J. Biol. Chem. 252, 5750-5755 (1977). (Pubitemid 8177750)
37. Nagatsu T, Ichinose H. Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin. Mol. Neurobiol. 19, 79-96 (1999). (Pubitemid 29174242)
38. Guillot TS, Miller GW. Protective actions of the vesicular monoamine transporter 2 (VMAT2) in monoaminergic neurons. Mol. Neurobiol. 39, 149-170 (2009).
39. Corti O, Sanchez-Capelo A, Colin P, et al. 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 (1999). (Pubitemid 29502868)
40. Kirik D, Georgievska B, Burger C, et al. 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 (2002). (Pubitemid 34286049)
41. Bjorklund T, Hall H, Breysse N, et al. Optimization of continuous in vivo DOPA production and studies on ectopic DA synthesis using rAAV5 vectors in Parkinsonian rats. J. Neurochem. 111, 355-367 (2009).
42. Bjorklund T, Carlsson T, Cederfjall EA, Carta M, Kirik D. 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 (2010).
43. Carlsson T, Winkler C, Burger C, et al. Reversal of dyskinesias in an animal model of Parkinson's disease by continuous l-DOPA delivery using rAAV vectors. Brain 128, 559-569 (2005). (Pubitemid 40380191)
44. Bankiewicz KS, Eberling JL, Kohutnicka M, et al. Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using prodrug approach. Exp. Neurol. 164, 2-14 (2000). (Pubitemid 30490717)
45. Bankiewicz KS, Forsayeth J, Eberling JL, et al. Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol. Ther. 14, 564-570 (2006). (Pubitemid 44296090)
46. Christine CW, Starr PA, Larson PS, et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 73, 1662-1669 (2009).
47. Eberling JL, Jagust WJ, Christine CW, et al. Results from a Phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology 70, 1980-1983 (2008).
48. Muramatsu S, Fujimoto K, Kato S, et al. A Phase I study of aromatic l-amino acid decarboxylase gene therapy for Parkinson's disease. Mol. Ther. 18, 1731-1735 (2010).
49. Azzouz M, Martin-Rendon E, Barber RD, et al. 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 (2002). (Pubitemid 35416868)
50. Sun M, Kong L, Wang X, et al. Coexpression of tyrosine hydroxylase, GTP cyclohydrolase I, aromatic amino acid decarboxylase, and vesicular monoamine transporter 2 from a helper virus-free herpes simplex virus type 1 vector supports high-level, long-term biochemical and behavioral correction of a rat model of Parkinson's disease. Hum. Gene Ther. 15, 1177-1196 (2004). (Pubitemid 40052431)
51. Shen Y, Muramatsu SI, Ikeguchi K, et al. 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 (2000). (Pubitemid 30670603)
52. Muramatsu S, Fujimoto K, Ikeguchi K, et al. 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 (2002). (Pubitemid 34251500)
53. Jarraya B, Boulet S, Ralph GS, et al. Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia. Sci. Transl Med. 1(2), 2ra4 (2009).
54. Bjorklund A, Bjorklund T, Kirik D. Gene therapy for dopamine replacement in Parkinson's disease. Sci. Transl Med. 1(2), 2ps2 (2009).
55. Feigin A, Kaplitt MG, Tang C, et al. Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease. Proc. Natl Acad. Sci. USA 104, 19559-19564 (2007).
56. Kaplitt MG, Feigin A, Tang C, et al. 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 (2007). (Pubitemid 46935946)
57. Laitinen LV, Bergenheim AT, Hariz MI. Leksell's posteroventral pallidotomy in the treatment of Parkinson's disease. J. Neurosurg. 76, 53-61 (1992).
58. Hassler R, Riechert T, Mundinger F, Umbach W, Ganglberger JA. Physiological observations in stereotaxic operations in extrapyramidal motor disturbances. Brain 83, 337-350 (1960).
59. Ohye C, Kubota K, Hongo T, Nagao T, Narabayashi H. Ventrolateral and subventrolateral thalamic stimulation. Motor effects. Arch. Neurol. 11, 427-434 (1964).
60. Follett KA, Weaver FM, Stern M, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease. N. Engl. J. Med. 362, 2077-2091 (2010).
61. Baron MS, Wichmann T, Ma D, DeLong MR. Effects of transient focal inactivation of the basal ganglia in parkinsonian primates. J. Neurosci. 22, 592-599 (2002). (Pubitemid 34049100)
62. Emborg ME, Carbon M, Holden JE, et al. Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. J. Cereb. Blood Flow Metab. 27, 501-509 (2007).
63. Luo J, Kaplitt MG, Fitzsimons HL, et al. Subthalamic GAD gene therapy in a Parkinson's disease rat model. Science 298, 425-429 (2002). (Pubitemid 35176353)
64. Lee B, Lee H, Nam YR, et al. Enhanced expression of glutamate decarboxylase 65 improves symptoms of rat parkinsonian models. Gene Ther. 12, 1215-1222 (2005). (Pubitemid 41136316)
65. Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260, 1130-1132 (1993). (Pubitemid 23186789)
66. Kotzbauer PT, Lampe PA, Heuckeroth RO, et al. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 384, 467-470 (1996). (Pubitemid 26414664)
67. Hoffer BJ, Hoffman A, Bowenkamp K, et al. Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo. Neurosci. Lett. 182, 107-111 (1994). (Pubitemid 24362034)
68. Tomac A, Lindqvist E, Lin LF, et al. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373, 335-339 (1995).
69. Kearns CM, Cass WA, Smoot K, Kryscio R, Gash DM. GDNF protection against 6-OHDA: time dependence and requirement for protein synthesis. J. Neurosci. 17, 7111-7118 (1997). (Pubitemid 27427888)
70. Sauer H, Rosenblad C, Bjorklund A. Glial cell line-derived neurotrophic factor but not transforming growth factor b 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion. Proc. Natl Acad. Sci. USA 92, 8935-8939 (1995).
71. Horger BA, Nishimura MC, Armanini MP, et al. Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J. Neurosci. 18, 4929-4937 (1998). (Pubitemid 28285401)
72. Rosenblad C, Kirik D, Devaux B, et al. 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 (1999). (Pubitemid 29192230)
73. Kirik D, Rosenblad C, Bjorklund A. Characterization of behavioral and neurodegenerative changes following artial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat. Exp. Neurol. 152, 259-277 (1998). (Pubitemid 28419264)
74. Sauer H, Oertel WH. Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat. Neuroscience 59, 401-415 (1994). (Pubitemid 24098798)
75. Lang AE, Gill S, Patel NK, et al. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann. Neurol. 59, 459-466 (2006). (Pubitemid 43358066)
76. Nutt JG, Burchiel KJ, Comella CL, et al. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 60, 69-73 (2003). (Pubitemid 36070646)
77. Salvatore MF, Ai Y, Fischer B, et al. Point source concentration of GDNF may explain failure of Phase II clinical trial. Exp. Neurol. 202, 497-505 (2006). (Pubitemid 44692690)
78. Patel NK, Gill SS. GDNF delivery for Parkinson's disease. Acta Neurochir. Suppl. 97, 135-154 (2007).
79. Fjord-Larsen L, Johansen JL, Kusk P, et al. Efficient in vivo protection of nigral dopaminergic neurons by lentiviral gene transfer of a modified Neurturin construct. Exp. Neurol. 195, 49-60 (2005). (Pubitemid 41116813)
80. Kordower JH, Herzog CD, Dass B, et al. 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 (2006). (Pubitemid 46048488)
81. Kordower JH, Emborg ME, Bloch J, et al. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 290, 767-773 (2000).
82. Choi-Lundberg DL, Lin Q, Chang YN, et al. Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 275, 838-841 (1997). (Pubitemid 27074886)
83. Eslamboli A, Georgievska B, Ridley RM, et al. Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson's disease. J. Neurosci. 25, 769-777 (2005). (Pubitemid 40170991)
84. Kirik D, Rosenblad C, Bjorklund A, Mandel RJ. 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 (2000). (Pubitemid 30396634)
85. Georgievska B, Kirik D, Rosenblad C, Lundberg C, Bjorklund A. Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector. Neuroreport. 13, 75-82 (2002). (Pubitemid 34102030)
86. Marks WJ Jr, Ostrem JL, Verhagen L, et al. 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 (2008).
87. Lo Bianco C, Deglon N, Pralong W, Aebischer P. Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease. Neurobiol. Dis. 17, 283-289 (2004). (Pubitemid 39345783)
88. Kirik D, Rosenblad C, Burger C, et al. Parkinson-like neurodegeneration induced by targeted overexpression of a-synuclein in the nigrostriatal system. J. Neurosci. 22, 2780-2791 (2002). (Pubitemid 37465827)
89. Klein RL, King MA, Hamby ME, Meyer EM. Dopaminergic cell loss induced by human A30P a-synuclein gene transfer to the rat substantia nigra. Hum. Gene. Ther. 13, 605-612 (2002). (Pubitemid 34264311)
90. Kirik D, Annett LE, Burger C, et al. Nigrostriatal a-synucleinopathy induced by viral vector-mediated overexpression of human a-synuclein: a new primate model of Parkinson's disease. Proc. Natl Acad. Sci. USA 100, 2884-2889 (2003). (Pubitemid 36297593)
91. Eslamboli A, Romero-Ramos M, Burger C, et al. Long-term consequences of human a-synuclein overexpression in the primate ventral midbrain. Brain 130, 799-815 (2007). (Pubitemid 46410741)
92. St Martin JL, Klucken J, Outeiro TF, et al. Dopaminergic neuron loss and up-regulation of chaperone protein mRNA induced by targeted over-expression of alpha-synuclein in mouse substantia nigra. J. Neurochem. 100, 1449-1457 (2007). (Pubitemid 46376202)
93. Lo Bianco C, Ridet JL, Schneider BL, Deglon N, Aebischer P. a-synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc. Natl Acad. Sci. USA 99, 10813-10818 (2002).
94. Maingay M, Romero-Ramos M, Kirik D. Viral vector mediated overexpression of human a-synuclein in the nigrostriatal dopaminergic neurons: a new model for Parkinson's disease. CNS Spectr. 10, 235-244 (2005). (Pubitemid 40489292)
95. Ulusoy A, Decressac M, Kirik D, Bjorklund A. Viral vector-mediated overexpression of a-synuclein as a progressive model of Parkinson's disease. Prog. Brain Res. 184, 89-111(2010).
96. Cha GH, Kim S, Park J, et al. Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. Proc. Natl Acad. Sci. USA 102, 10345-10350 (2005). (Pubitemid 41023373)
97. Hasegawa T, Treis A, Patenge N, et al. Parkin protects against tyrosinase-mediated dopamine neurotoxicity by suppressing stress-activated protein kinase pathways. J. Neurochem. 105, 1700-1715 (2008). (Pubitemid 351678502)
98. Imai Y, Soda M, Takahashi R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J. Biol. Chem. 275, 35661-35664 (2000).
99. Poole AC, Thomas RE, Andrews LA, et al. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc. Natl Acad. Sci. USA 105, 1638-1643 (2008). (Pubitemid 351346567)
100. Suen DF, Narendra DP, Tanaka A, Manfredi G, Youle RJ. Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. Proc. Natl Acad. Sci. USA (2010).
101. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 183, 795-803 (2008).
102. Lo Bianco C, Schneider BL, Bauer M, et al. Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an a-synuclein rat model of Parkinson's disease. Proc. Natl Acad. Sci. USA 101, 17510-17515 (2004). (Pubitemid 39657434)
103. Yamada M, Mizuno Y, Mochizuki H. Parkin gene therapy for a-synucleinopathy: a rat model of Parkinson's disease. Hum. Gene Ther. 16, 262-270 (2005). (Pubitemid 40344217)
104. Manfredsson FP, Burger C, Sullivan LF, et al. 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 (2007). (Pubitemid 47429661)
105. Vercammen L, Van der Perren A, Vaudano E, et al. Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's disease. Mol. Ther. 14, 716-723 (2006). (Pubitemid 44507714)
106. Paterna JC, Leng A, Weber E, Feldon J, Bueler H. DJ-1 and parkin modulate dopamine-dependent behavior and inhibit MPTP-induced nigral dopamine neuron loss in mice. Mol. Ther. 15, 698-704 (2007). (Pubitemid 46431989)
107. Grimm D. Small silencing RNAs: state-of-the-art. Adv. Drug Deliv. Rev. 61, 672-703 (2009).
108. Ralph GS, Radcliffe PA, Day DM, et al. Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model. Nat. Med. 11, 429-433 (2005). (Pubitemid 40562334)
109. Raoul C, Abbas-Terki T, Bensadoun JC, et al. Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS. Nat. Med. 11, 423-428 (2005). (Pubitemid 40562333)
110. Rodriguez-Lebron E, Denovan-Wright EM, Nash K, Lewin AS, Mandel RJ. Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice. Mol. Ther. 12, 618-633 (2005). (Pubitemid 41350143)
111. Alves S, Nascimento-Ferreira I, Auregan G, et al. Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado-Joseph disease. PLoS ONE 3, e3341 (2008).
112. Harper SQ, Staber PD, He X, et al. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc. Natl Acad. Sci. USA 102, 5820-5825 (2005). (Pubitemid 40559643)
113. DiFiglia M, Sena-Esteves M, Chase K, et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc. Natl Acad. Sci USA 104, 17204-17209 (2007). (Pubitemid 350211015)
114. Sapru MK, Yates JW, Hogan S, et al. Silencing of human a-synuclein in vitro and in rat brain using lentiviral-mediated RNAi. Exp. Neurol. 198(2), 382-390 (2006).
115. McCormack AL, Mak SK, Henderson JM, et al. a-synuclein suppression by targeted small interfering RNA in the primate substantia nigra. PLoS ONE 5, e12122 (2010).
116. Gorbatyuk OS, Li S, Nash K, et al. In vivo RNAi-mediated a-synuclein silencing induces nigrostriatal degeneration. Mol. Ther. 18(8), 1450-1457 (2010).
117. Perez RG, Waymire JC, Lin E, et al. A role for a-synuclein in the regulation of dopamine biosynthesis. J. Neurosci. 22, 3090-3099 (2002). (Pubitemid 35379198)
118. Alerte TN, Akinfolarin AA, Friedrich EE, et al. a-synuclein aggregation alters tyrosine hydroxylase phosphorylation and immunoreactivity: lessons from viral transduction of knockout mice. Neurosci. Lett. 435, 24-29 (2008).
119. Frey KA, Koeppe RA, Kilbourn MR, et al. Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging. Ann. Neurol. 40, 873-884 (1996). (Pubitemid 27044605)
120. Volles MJ, Lee SJ, Rochet JC, et al. Vesicle permeabilization by protofibrillar a-synuclein: implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry 40, 7812-7819 (2001). (Pubitemid 32622972)
121. Lotharius J, Brundin P. Impaired dopamine storage resulting from a-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum. Mol. Genet. 11, 2395-2407 (2002). (Pubitemid 35174703)
122. Lee FJ, Liu F, Pristupa ZB, Niznik HB. Direct binding and functional coupling of a-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis. FASEB J. 15, 916-926 (2001). (Pubitemid 32290778)
123. Wersinger C, Prou D, Vernier P, Sidhu A. Modulation of dopamine transporter function by a-synuclein is altered by impairment of cell adhesion and by induction of oxidative stress. FASEB J. 17, 2151-2153 (2003).
124. Wersinger C, Vernier P, Sidhu A. Trypsin disrupts the trafficking of the human dopamine transporter by a-synuclein and its A30P mutant. Biochemistry 43, 1242-1253 (2004). (Pubitemid 38176522)
125. Lewis J, Melrose H, Bumcrot D, et al. In vivo silencing of a-synuclein using naked siRNA. Mol. Neurodegener. 3, 19 (2008).
126. Specht CG, Schoepfer R. Deletion of the a-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci. 2, 11 (2001).
127. Jackson AL, Burchard J, Schelter J, et al. Widespread siRNA 'off-target' transcript silencing mediated by seed region sequence complementarity. RNA 12, 1179-1187 (2006). (Pubitemid 43990543)
128. Denovan-Wright EM, Rodriguez-Lebron E, Lewin AS, Mandel RJ. Unexpected off-targeting effects of anti-huntingtin ribozymes and siRNA in vivo. Neurobiol. Dis. 29, 446-455 (2008).
129. Grimm D, Streetz KL, Jopling CL, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441, 537-541 (2006). (Pubitemid 44050158)
130. Castanotto D, Sakurai K, Lingeman R, et al. Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC. Nucleic Acids Res. 35, 5154-5164 (2007). (Pubitemid 47394199)
131. Ehlert EM, Eggers R, Niclou SP, Verhaagen J. Cellular toxicity following application of adeno-associated viral vector-mediated RNA interference in the nervous system. BMC Neurosci. 11, 20 (2010).
132. McBride JL, Boudreau RL, Harper SQ, et al. Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi. Proc. Natl Acad. Sci. USA 105, 5868-5873 (2008). (Pubitemid 351758464)
133. Ulusoy A, Sahin G, Bjorklund T, Aebischer P, Kirik D. Dose optimization for long-term rAAV-mediated RNA interference in the nigrostriatal projection neurons. Mol. Ther. 17, 1574-1584 (2009).
134. Ulusoy A, Sahin G, Kirik D. Presynaptic dopaminergic compartment determines the susceptibility to l-DOPA-induced dyskinesia in rats. Proc. Natl Acad. Sci. USA. (2010).
135. Wood MJ, Charlton HM, Wood KJ, Kajiwara K, Byrnes AP. Immune responses to adenovirus vectors in the nervous system. Trends Neurosci. 19, 497-501 (1996). (Pubitemid 26359868)
136. Kajiwara K, Byrnes AP, Charlton HM, Wood MJ, Wood KJ. Immune responses to adenoviral vectors during gene transfer in the brain. Hum. Gene Ther. 8, 253-265 (1997). (Pubitemid 27412261)
137. Hardy S, Kitamura M, Harris-Stansil T, Dai Y, Phipps ML. Construction of adenovirus vectors through Cre-lox recombination. J. Virol. 71, 1842-1849 (1997). (Pubitemid 27078561)
138. Morral N, O'Neal W, Rice K, et al. Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons. Proc. Natl Acad. Sci. USA 96, 12816-12821 (1999). (Pubitemid 29513585)
139. Sandig V, Youil R, Bett AJ, et al. Optimization of the helper-dependent adenovirus system for production and potency in vivo. Proc. Natl Acad. Sci. USA 97, 1002-1007 (2000). (Pubitemid 30080802)
140. Lau AA, Hopwood JJ, Kremer EJ, Hemsley KM. SGSH gene transfer in mucopolysaccharidosis type IIIA mice using canine adenovirus vectors. Mol. Genet. Metab. 100, 168-175 (2010).
141. Krenz A, Falkenburger BH, Gerhardt E, Drinkut A, Schulz JB. Aggregate formation and toxicity by wild-type and R621C synphilin-1 in the nigrostriatal system of mice using adenoviral vectors. J. Neurochem. 108, 139-146 (2009).
142. Corsetti V, Amadoro G, Gentile A, et al. Identification of a caspase-derived N-terminal tau fragment in cellular and animal Alzheimer's disease models. Mol. Cell Neurosci. 38, 381-392 (2008).
143. Dormond E, Meneses-Acosta A, Jacob D, et al. An efficient and scalable process for helper-dependent adenoviral vector production using polyethylenimine-adenofection. Biotechnol. Bioeng. 102, 800-810 (2009).
144. Grimm D, Kay MA, Kleinschmidt JA. 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 (2003). (Pubitemid 36790261)
145. Kay MA, Nakai H. Looking into the safety of AAV vectors. Nature 424(6946), 251 (2003).
146. Peden CS, Burger C, Muzyczka N, Mandel RJ. Circulating anti-wild-type adeno-associated virus type 2 (AAV2) antibodies inhibit recombinant AAV2 (rAAV2)-mediated, but not rAAV5-mediated, gene transfer in the brain. J. Virol. 78, 6344-6359 (2004). (Pubitemid 38715933)
147. Markakis EA, Vives KP, Bober J, et al. Comparative transduction efficiency of AAV vector serotypes 1-6 in the substantia nigra and striatum of the primate brain. Mol. Ther. 18, 588-593 (2010).
148. Naldini L, Blomer U, Gallay P, et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263-267 (1996). (Pubitemid 26119138)
149. Cornu TI, Cathomen T. Targeted genome modifications using integrase-deficient lentiviral vectors. Mol. Ther. 15, 2107-2113 (2007). (Pubitemid 350148926)
150. Lombardo A, Genovese P, Beausejour CM, et al. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat. Biotechnol. 25, 1298-1306 (2007). (Pubitemid 350076515)
151. Vargas J Jr, Gusella GL, Najfeld V, Klotman ME, Cara A. Novel integrase-defective lentiviral episomal vectors for gene transfer. Hum. Gene Ther. 15, 361-372 (2004). (Pubitemid 38469778)
152. Sarkis C, Philippe S, Mallet J, Serguera C. Non-integrating lentiviral vectors. Curr. Gene Ther. 8, 430-437 (2008).
153. Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat. Biotechnol. 15, 871-875 (1997).
154. Dull T, Zufferey R, Kelly M, et al. A third-generation lentivirus vector with a conditional packaging system. J. Virol. 72, 8463-8471 (1998). (Pubitemid 28471781)
155. Miyoshi H, Blomer U, Takahashi M, Gage FH, Verma IM. Development of a self-inactivating lentivirus vector. J. Virol. 72, 8150-8157 (1998).
156. Zufferey R, Dull T, Mandel RJ, et al. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J. Virol. 72, 9873-9880 (1998). (Pubitemid 28520853)
157. Deglon N, Tseng JL, Bensadoun JC, et al. Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson's disease. Hum. Gene Ther. 11, 179-190 (2000). (Pubitemid 30044050)
158. Hannon GJ, Rossi JJ. Unlocking the potential of the human genome with RNA interference. Nature 431, 371-378 (2004). (Pubitemid 39265678)
159. Carthew RW. Molecular biology. A new RNA dimension to genome control. Science 313, 305-306 (2006) (Pubitemid 44480942)
160. ClinicalTrials.gov identifier: NCT00229736. www.clinicaltrials.gov/ct2/ show/NCT00229736
161. ClinicalTrials.gov identifier: NCT00627588. www.clinicaltrials.gov/ct2/ show/NCT00627588
162. ClinicalTrials.gov identifier: NCT00252850. www.clinicaltrials.gov/ct2/ show/NCT00252850
163. ClinicalTrials.gov identifier: NCT00400634. www.clinicaltrials.gov/ct2/ show/NCT00400634
164. Ceregene announces clinical data from Phase II clinical trial of CERE-120 for Parkinson's disease. www.ceregene.com/press-112608.asp
165. Ceregene presents additional clinical data from Phase II trial of CERE-120 for Parkinson's disease. www.ceregene.com/press-052709.asp