Adeno-associated virus (AAV) vectors in the CNS

Current Gene Therapy

Volumn 11, Issue 3, 2011, Pages 181-188

  McCown, Thomas J ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

AAV; Gene therapy; Neurological disorders; Viral vectors

Indexed keywords

ADENO ASSOCIATED VIRUS 2 5 VECTOR; ADENO ASSOCIATED VIRUS 9 GREEN FLUORESCENT PROTEIN; ADENO ASSOCIATED VIRUS 9 VECTOR; ADENO ASSOCIATED VIRUS GLIAL CELL LINE NEUROTROPHIC FACTOR VECTOR; ADENOSINE KINASE; ALPHA N ACETYLGLUCOSAMINIDASE; ANTISENSE OLIGODEOXYNUCLEOTIDE; AROMATIC LEVO AMINO ACID DECARBOXYLASE; ASPARTOACYLASE; BETA GLUCURONIDASE; BRAIN DERIVED NEUROTROPHIC FACTOR; DIPEPTIDYL PEPTIDASE; GALANIN; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GLUTAMATE DECARBOXYLASE; GREEN FLUORESCENT PROTEIN; GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE I; NERVE GROWTH FACTOR; NEUROPEPTIDE Y; NEURTURIN; POLYGLUTAMINE; RECOMBINANT ADENO ASSOCIATED VIRUS VECTOR; TYROSINE 3 MONOOXYGENASE; UNCLASSIFIED DRUG; VIRUS VECTOR;

ADENO ASSOCIATED VIRUS; ALZHEIMER DISEASE; ANTISENSE THERAPY; ANTISENSE VECTOR; ARTICLE; BLOOD BRAIN BARRIER; CANAVAN DISEASE; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL EFFECTIVENESS; DISEASE MODEL; EPILEPSY; GENE AMPLIFICATION; GENE EXPRESSION; GENE SILENCING; HUMAN; HUNTINGTON CHOREA; IN VIVO STUDY; KENNEDY DISEASE; MUCOPOLYSACCHARIDOSIS; NEURONAL CEROID LIPOFUSCINOSIS; NONHUMAN; PARKINSON DISEASE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; SEIZURE; SPINOCEREBELLAR DEGENERATION; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; VIRAL TROPISM;

ADENO-ASSOCIATED VIRUS; ADENO-ASSOCIATED VIRUS - 2;

EID: 79958191163     PISSN: 15665232     EISSN: 18755631     Source Type: Journal    
DOI: 10.2174/156652311795684759     Document Type: Article

References (103)

1. Samulski, RJ, Chang, LS, Shenk, T. Helper-free stocks of adenoassociated viruses: normal integration does not require viral gene expression. J Virol 1989; 63: 3822-28.
2. Kaplitt, MG, Leone, P, Samulski, RJ, et al.Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Na. Genet 1994; 8: 148-54.
3. McCown, TJ, Xiao, X, Li, J, et al.Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res 1996; 713: 99-107.
4. During, MJ, Samulski, RJ, Elsworth, JD, et al.In vivo expression of therapeutic human genes for dopamine production in the caudatesof MPTP-treated monkeys using an AAV vector. Gene Ther 1998; 5: 820-7.
5. Bankiewicz, KS, Eberling, JL, Kohutnicka, M, et al.Convectionenhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol 2000; 164: 2-14.
6. Chen, H, McCarty, DM, Bruce, AT, et al.Gene Transfer and expression in oligodendrocytes under the control of myelin basic protein transcriptional control region mediated by adeno-associated virus. Gene Ther 1998; 5: 50-58.
7. Weller, ML, Stone, IM, Goss, A, et al., Selective overexpression of excitatory amino acid transporter 2)EAAT2) in astrocytes enhances neuroprotection from moderate but not severe hypoxiaischemia. Neurosci 2008; 155:1204-1211.
8. Lawlor, PA, Bland, RJ, Mouravlev, A, et al.Efficient gene delivery and selective transduction of glial cells in the mammalian brain by AAV serotypes isolated from nonhuman primates. Mol Ther 2009; 17: 1692-1702.
9. Klein, RL, Muir, D, King, MA, et al.Long-term actions of vectorderived nerve growth factor or brain-derived neurotrophic factor on choline acetyltransferase and Trk receptor levels in the adult rat basal forebrain. Neurosci 1999; 90: 815-821.
10. Klein, RL, Meyer, EM, Peel, AL, et al.Neuron-specific transduction in the rat septohippocampal or nigrostriatal pathway by recombinant adeno-associated virus vectors. Exp Neurol 1998; 150: 183-194.
11. Haberman, RP, Criswell, HE, Snowdy, S, et al.Therapeutic liabilities of in vivo viral vector tropism: adeno-associated virus (AAV) vectors, NMDAR 1 antisense and focal seizure sensitivity. Mol Ther 2002; 6: 495-500.
12. Haberman, RP, McCown, TJ, Samulski, R.J. Inducible long-term gene expression in brain with adeno-associated virus gene transfer. Gene Ther 1998; 5: 1604-11.
13. Haberman, RP, McCown, TJ, Samulski, R.J. Novel transcriptional signals in the adeno-associated virus terminal repeat A/D junction element. J Virol 2000; 74: 8732-39.
14. Fitzsimons, HL, McKenzie, JM, During, MJ. Insulators coupled to a minimal bidirectional tet cassette for tight regulation of rAAVmediated gene transfer in the mammalian brain. Gene Ther 2001; 8: 1675-1681.
15. Jiang, L, Rampalli, S, George, D, et al.Tight regulation from a single tet-off rAAV vector as demonstrated by flow cytometry and quantitative, real-time PCR. Gene Ther 2004; 11: 1057-1067.
16. Rivera, VM, Ye, X, Courage, NL, et al.Long-term regulated expression of growth hormone in mice after intramuscular gene transfer. Proc Nat Acad Sci USA 1999; 96: 8657-8662.
17. Haberman, RP, Samulski, RJ, McCown, TJ. Attenuation of seizures and neuronal death by adeno-associated virus (AAV) vector galanin expression and secretion. Nat Med 2003; 9: 1076-1080.
18. Chtarto, A, Yang, X, Bockstael, O, et al.Controlled delivery of glial cell line-derived neurotrophic factor by a single tetracyclineinducible AAV vector. Exp Neurol 2007; 204: 387-399.
19. Manfredsson, FP, Burger, C, Rising, AC. et al.Tight long-term dynamic doxycycline responsive nigrostriatal GDNF using a single rAAV vector. Mol. Ther. 2009; 17: 1857-1867.
20. Chiorini, JA, Rang, L, Liu, Y, et al., Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV particles. J Virol 1997; 71: 6823-6833.
21. Chiorini, JA, Kim, F, Yang, L. Cloning and characterization of adeno-associated virus type 5. J Virol 1999; 73: 1309-1319.
22. Xiao, W, Chirmule, N, Berta, SC, et al.Gene therapy vectors based on adeno-associated virus type 1. J Virol 1999; 73: 3994-4003.
23. Davidson, BL, Stein, CS, Heth, JA, et al.Recombinant adenoassociated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system. Proc Natl Acad Sci USA 2000; 97: 3428-32.
24. Mastakov, MY, Baer, K, Symes, CW. et al.Immunological aspects of recombinant adeno-associated virus delivery to the mammalian brain. J Virol 2002; 76: 8446-8454.
25. Chao, H, Lui, Y, Rabinowitz, J, et al., Several log increase in therapeutic transgene delivery by distinct adeno-associated viral serotype vectors. Mol Ther 2000; 2: 619-623.
26. Rabinowitz, JE, Rolling, F, Li, C, et al.Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity. J Virol 2002; 76: 791-801.
27. Burger, C, Gorbatyuk, OS, Velardo, MJ, et al.Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol Ther 2004; 10: 302-317.
28. Gao, GP, Alvira, MR, Wang, L, et al.Novel adeno-associated vectors from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci USA 2002; 99: 11854-11859.
29. Gao, G, Vandenberghe, LH, Wilson, JM. New recombinant serotypes of AAV vectors. Curr Gene Ther 2005; 5: 285-297.
30. Foust, KD, Nurre, E, Montgomery, CL. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol 2009; 27: 59-65.
31. Foust, KD, Wang, X, McGovern, VL, et al.Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat. Biotechnol. 2010; 28: 271-274.
32. Duque, S, Joussemet, B, Riviere, C, et al.Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol Ther 2009; 17: 1187-1196.
33. Maheshri, N, Koerber, JT, Kaspar, BK, et al.Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nat Biotechnol 2006; 24: 198-204.
34. Wu, Z, Asokan, A, Grieger, JC, et al.Single amino acid changes can influence titer, heparin binding, and tissue tropism in different adeno-associated virus serotypes. J Virol 2006; 80: 11393-11397.
35. Li, W, Asokan, A, Wu, Z, et al.Engineering and Selection of Shuffled AAV Genomes: A New Strategy for Producing Targeted Biological Nanoparticles. Mol Ther 2008; 16: 1252-1260.
36. Asokan, A, Conway, JC, Phillips, JL, et al.Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle. Nat Biotech 2010; 28: 79-82.
37. Bowles, DE, Li, C, Rabinowitz, JE, et al.The hybrid AAV2.5 vector transduces neurons bordering the third and fourth ventricles after lateral ventricular infusion in rats. Am. Soc. Gene and Cell Ther. 13th Annual Meeting 2010; Abstract [#366], page 109.
38. Zhong, L, Li, B, Mah, CS, et al.Next generation of adenoassociated virus 2 vectors: point mutations intyrosines lead to highefficiency transduction at lower doses. Proc Nat Acad Sci 2008; 105: 7827-7832.
39. Li, W, Asokan, A, Wu, Z, et al.Engineering and selection of shuffled AAV genomes: a new strategy for producing targeted biological nanoparticles. Mol Ther 2008; 16: 1252-1260.
40. Gray, SJ, Blake, BL, Criswell, HE, et al.Directed evolution of a novel adeno-associated virus (AAV) vector that crosses the seizure compromised blood-brain barrier (BBB). Mol Ther 2010; 18: 570-578.
41. Blacklow, NR, Hoggan, MD, Rowe, WP. Serologic evidence for human infections with adenovirus-associated viruses. J Natl Cancer Inst 1968; 40: 319-327.
42. Blacklow, NR, Hoggan. MD, Sereno, MS, et al.A seroepidemiologic study of adenovirus-associated virus infection in infants and children. Am J Epidemiol 1971; 94: 359-366.
43. Chirmule, NK, Propert, K, Magosin, S, et al.Immune responses to adenovirus and adeno-associated virus in humans. Gene Ther 199; 6: 1574-1583.
44. Erles, KP, Sebokva, P, Schlehofer, JR. Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus. J Med Virol 1999; 59: 406-411.
45. Boutin, S, Monteilhet, V, Veron, P, et al.Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther 2010; 21: 704-712.
46. Lo, WD, Qu, G, Sferra, TJ, et al.Adeno-associated virus-mediated gene transfer to the brain: duration and modulation of expression. Hum Gene Ther 1999; 10: 201-213.
47. Mastakov, MY, Baer, K, Symes, CW, et al.Immunological aspects of recombinant adeno-associated virus delivery to the mammalian brain. J Virol 2002; 76: 8446-8454.
48. Peden, CS, Burger, C, Muzyczka, N, et al.Circulating anti-wildtype adeno-associated virus type 2 (AAV2) antibodies inhibit recombinant AAV 2 (rAAV2)-mediated, but not rAAV5-mediated, gene transfer in the brain. J Virol 2004; 78: 6344-6359.
49. Sanftner, LM, Suzuki, BM, Doroudchi, MM, et al.Striatal deliveryof rAAV-hAADC to rats with preexisting immunity to AAV. Mol Ther 2004; 9: 403-409.
50. Hasbrouck, NC, High, KA. AAV-mediated gene transfer for the treatment of hemophilia B: problems and prospects. Gene Ther 2008; 15: 870-875.
51. Hadaczek, P, Eberling JL, Pivirotto, P, et al.Eight years of clnical improvement in MPTP-lesioned primates after gene therapy with AAV2-hAADC. Mol. Ther 2010; 18: 1458-1461.
52. Hadaczek, P, Forsayeth, J, Mirek, H, et al.Transduction of nonhuman primate brain with adeno-associated virus serotype 1: vector trafficking and immune response. Human Gen Ther 2009; 20: 225-237.
53. Mandel, RJ, Rendahl, KG, Spratt, SK, et al.Characterization of intrastriatal recombinant adeno-associated virus-mediated gene transfer of human tyrosine hydroxylase and human GTPcyclohydrolase I in a rat model of Parkinson's disease. J Neurosci 1998; 18: 4271-84.
54. 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. Hu. Gene Ther 2000; 11: 1509-5119.
55. Choi-Lundberg, DL, Lin, Q, Yung-Nien, C, et al.Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 1997; 273: 838-841.
56. Mandel, RJ, Spratt, SK, Snyder, RO, et al.Midbrain injection of recombinant adeno-associated virus encoding rat glial cell linederived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson's disease in rats. Proc Natl Acad Sci USA 1997; 94: 14083-14088.
57. Eslamboli, A, Cummings, RM, Ridley, RM, et al.Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides protection against 6-OHDA lesion in the common marmoset monkey (Callithrix jacchus). Exp Neurol 2003; 184: 536-548.
58. Kirik, D, Rosenblad, C, Bjorklund, A, et al.Long-term rAAVmediated 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 2000; 20: 4686-4700.
59. Eslamboli, A, Georgievska, B, Ridley, RM, et al.Continuous lowlevel 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 Neuroscience 2005; 25: 769-777.
60. Luo, J, Kaplitt, MG, Fitzsimons, HL, et al.Subthalamic GAD gene therapy in a parkinson's disease rat model. Science 2002; 298: 425-429.
61. LeWitt, PA, Rezai, AR, Leehey, MA, et al.AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, shamsurgery controlled, randomized trial. The Lancet 2011; 10: 309-319.
62. Watson, GL, Sayles, JN, Chen, C, et al.Treatment of lysosomal storage disease in MPS VII mice using a recombinant adenoassociated virus. Gene Ther 1998; 5: 1642-1649
63. Daly, TM, Vogler, C, Levy, B, et al.Neonatal gene transfer leads to widespread correction of pathology in a murine model of lysosomal storage disease. Proc Natl Acad Sci USA 1999; 96: 2296-22300
64. Skorupa, AF, Fisher, KJ, Wilson, JM, et al.Sustained production of beta-glucuronidase from localized sites after AAV vector gene transfer results in widespread distribution of enzyme and reversal of lysosomal storage lesions in a large volume of brain in mucopolysaccharidosis VII mice. Exp Neurol 1999; 160: 17-27.
65. Nguyen, JB, Sanchez-Pernaute, R, Cunningham, J, et al.Convection-enhanced delivery of AAV-2 combined with heparin increases TK gene transfer in the rat brain. Neuroreport 2001; 12: 1961-1964.
66. Mastakov, MY, Baer, K, Xu, R, et al.Combined injection of rAAV with mannitol enhances gene expression in the rat brain. Mol. Ther. 2001; 3: 225-232.
67. Mastikov, MY, Baer, K, Kotin, RM, Recombinant adenoassociated virus serotypes 2- and 5-mediated gene transfer in the mammalian brain: quantitative analysis of heparin co-infusion. Mol Ther 2002; 5: 371-380.
68. Hadaczek, P, Mirek, H, Bringas, J, et al.Basic fibroblast growth factor enhances transduction, distribution and axonal ransport of adeno-associated virus type 2 vector in rat brain. Human Gene Ther 2004; 15: 469-479.
69. Matalon, R, Surendran, S, Rady, PL, et al.Adeno-associated virusmediated aspartoacylase gene transfer to the brain of knockout mouse for canavan disease. Mol Ther 2003; 7: 580-587.
70. Janson, C, McPhee, S, Bilaniuk, L, et al.Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. Hum Gene Ther 2002; 13: 1391-1412.
71. Mandel, RJ, Gage, FH, Clevenger, DG, et al.Nerve growth factor expressed in the medial septum following in vivo gene delivery using a recombinant adeno-associated viral vector protects cholinergic neurons from fimbria-fornix lesion-induced degeneration. Exp Neurol 1999; 155: 59-64.
72. Klein, RL, Hirko, AC, Meyers, CA, et al.NGF gene transfer to intrinsic basal forebrain neurons increases cholinergic cell size and protects from age-related, spatial memory deficits in middle-aged rats. Brain Res 2000; 875: 144-151
73. McCown, T.J. Adeno-associated virus-mediated expression and constitutive secretion of galanin suppresses limbic seizure activity in vivo. Mol Ther 2006; 14: 63-68.
74. Richichi, C, Lin, EJ, Stefanin, D, et al.Anticonvulsant and antiepileptogenic effects mediated by adeno-associated virus vector neuropeptide Y expression in the rat hippocampus. J Neurosci 2004; 24: 3051-3059.
75. Noè, F, Pool, AH, Nissinen, J, et al.Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy. Brain 2008; 131:1506-1515.
76. Xia, H, Mao, Q, Eliason, SOL, et al.RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med 2004; 10: 816-820.
77. Theofilas, P, Brar, S, Stewart KA, et al.Adenosine kinase as a target for therapeutic antisense strategies in epilepsy. Epilepsia 2011; 52: 589-601.
78. Xiao, X, McCown, TJ, Li, J, et al.Adeno-associated virus (AAV) vector antisense gene transfer in vivo decreases GABAA α1 containing receptors and increases collicular seizure sensitivity. Brain Res. 1997; 576: 76-83.
79. Klein, RL, McNamara, RK, King, MA, et al.Generation of aberrant sprouting in the adult rat brain by GAP-43 somatic gene transfer. Brain Res. 1999; 832: 136-44.
80. Mochizuki, H, Hayakawa, H, Migita, M, et al.An AAV-derived Apaf-1 dominant negative inhibitor prevents MPTP toxicity as antiapoptotic gene therapy for Parkinson's disease. Proc Nat Acad Sci USA 2001; 98: 10918-23.
81. South, SMO, Kohno, T, Kaspar, BK, et al.A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain. J Neurosci 2003; 23: 5031-5040.
82. Klein, RL, King, MA, Hamby, ME, et al.Dopaminergic cell loss induced by human A30P alpha-synuclein gene transfer to the rat substantia nigra. Hum Gene Ther 2002; 13: 605-612.
83. Kirk, D, Rosenblad, C, Burger, C, et al.Parkinson-like neurodegenration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 2002; 22: 2780-2791.
84. Gorbatyuk, OS, Li, S, Sullivan, LF, et al.The phosphorylation state of ser-129 in human alpha-synuclein etermines neurodegeneration in a rat model of Parkinson disease. Proc Nat Acad Sci 2008; 105: 763-768.
85. Wang, DB, Dayton, RD, Henning, PP, et al.Expansive gene transfer in the rat CNS rapidly produces amyotrophic lateral sclerosis relevant sequelae when TDP-43 is overexpressed. Mol Ther 2010; 18: 2064-2074.
86. Eberling, JL, Jagust, WJ, Christine, CW, et al.Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurol 2008; 70: 1980-1983.
87. 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 2010; 18: 1731-1735.
88. 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 2007; 369: 2097-2105.
89. Gasmi M, Herzog, CD, Brandon, EP, et al.Striatal delivery of neurturin by CERE-120, an AAV 2 vector for the treatment of dopaminergic neuron degeneration in Parkinson's disease. Mol Ther 2007; 15: 62-68.
90. Herzog, CD, Dass, B, Holden, JE, et al.Striatal delivery of CERE-120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys. Mov Disord 2007; 22: 1124-1132.
91. 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 2008; 7: 400-408.
92. Passini, MA, Watson, DJ, Vite, CH, et al.Intraventricular brain injections of adeno-associated virus type 1 (AAV1) in neonatal mice results in complementary patterns of neuronal transduction to AAV 2 and total long-term correction of storage lesions in the brains of beta-glucuronidase-deficient mice. J Virol 2003; 77:7034-7040.
93. Fu, H, Samulski, RJ, McCown, TJ, et al.Neurological correction of lysosomal storage in a mucopolysaccharidosis IIIB mouse model by adeno-associated virus-mediated gene delivery. Mol Ther 2002; 5: 42-49.
94. Fu, H, Kang, L, Jennings, JS, et al.Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice. Gene Ther 2007; 14: 1065-1077.
95. Tuszynski, MH, Thal, L, Pay, M, et al.A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 2005; 11: 551-555.
96. Nagahara, AH, Merrill, DA, Coppola, G, et al.Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med 2009; 15: 331-337.
97. Sondhi, D, Peterson, DA, Edelstein, AM, et al.Survival advantage of neonatal CNS gene transfer for late infantile neuronal ceroid lipofuscinosis. Exp. Neurol. 2008; 213: 18-27.
98. Souweidane, MM, Fraser, JF, Arkin, LM, et al.Gene Therapy for late infantile neuronal ceroid lipofuscinosis neurosurgical considerations. J Neurosurg Pediatr 2010; 6: 115-122.
99. McBride, JL, During, MJ, Wu, J, et al.Structural and functional neuroprotection in a rat model of Huntington's disease by viral gene transfer of GDNF. Exp Neurol 2003; 181: 213-223.
100. Kells, AP, Fong, DM, Dragunow, M, et al.AAV-mediated gene delivery of BDNF or GDNF is neuroprotective in a model of Huntington disease. Mol Therapy 2004; 9: 1405-1423.
101. Franich, NR, Fitzsimmons, HL, Fong, DM, et al.AAV vectormediated RNAi of mutant huntingtin expression is neuroprotective in a novel genetic rat model of Huntington's. Mol Ther 2008; 16: 947-956.
102. Ramaswamy, S, McBride, JL, Han, I, et al.Intrastriatal CERE-120 (AAV-neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease. Neurobiol Dis 2009; 34: 40-50.
103. Boudreau, RL, McBride, JL, Martins, I, et al.Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice. Mol. Ther 2009; 17: 1053-1063.