Gene Therapy for Misfolding Protein Diseases of the Central Nervous System

Neurotherapeutics

Volumn 10, Issue 3, 2013, Pages 498-510

  San Sebastian, Waldy ^a   Samaranch, Lluis ^a   Kells, Adrian P ^a   Forsayeth, John ^a   Bankiewicz, Krystof S ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Adeno associated virus; CSF delivery; Gene therapy; Misfolding protein; MRI guided delivery

Indexed keywords

MEMBRANE METALLOENDOPEPTIDASE; PROTEIN; SHORT HAIRPIN RNA;

ADAPTIVE IMMUNITY; ALZHEIMER DISEASE; CENTRAL NERVOUS SYSTEM DISEASE; CEREBROSPINAL FLUID; CISTERNA MAGNA; GENE DELIVERY SYSTEM; GENE TARGETING; GENE THERAPY; GLOBUS PALLIDUS; HUMAN; HYPODERMIC NEEDLE; IMMUNE RESPONSE; NERVE FIBER TRANSPORT; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN UNFOLDING; REVIEW; SUBSTANTIA NIGRA; SUBTHALAMIC NUCLEUS; TRANSGENE; VIRUS PARTICLE;

ANIMALS; CENTRAL NERVOUS SYSTEM DISEASES; GENETIC THERAPY; HUMANS; PROTEOSTASIS DEFICIENCIES;

EID: 84879893250     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-013-0191-8     Document Type: Review

References (152)

1. Kaganovich D, Kopito R, Frydman J. Misfolded proteins partition between two distinct quality control compartments. Nature 2008;454: 1088-1095.
2. Roth J, Yam GH, Fan J, et al., Protein quality control: the who's who, the where's and therapeutic escapes. Histochem Cell Biol 2008;129: 163-177.
3. Luheshi LM, Dobson CM, Bridging the gap: from protein misfolding to protein misfolding diseases. FEBS Lett 2009;583: 2581-2586.
4. Chiti F, Dobson CM. Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 2006;75: 333-366.
5. Bellotti V, Mangione P, Stoppini M. Biological activity and pathological implications of misfolded proteins. Cell Mol Life Sci 1999;55: 977-991.
6. Dobson CM. Protein misfolding, evolution and disease. Trend Biochem Sci 1999;24: 329-332.
7. Kalia SK, Kalia LV, McLean PJ. Molecular chaperones as rational drug targets for Parkinson's disease therapeutics. CNS Neurol Disord Drug Targets 2010;9: 741-753.
8. Neef DW, Jaeger AM, Thiele DJ. Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat Rev Drug Discov 2011;10: 930-944.
9. Richardson RM, Varenika V, Forsayeth JR, et al. Future applications: gene therapy. Neurosurg Clin North Am 2009;20: 205-210.
10. Mandel RJ, Burger C, Snyder RO. Viral vectors for in vivo gene transfer in Parkinson's disease: properties and clinical grade production. Exp Neurol 2008;209: 58-71.
11. Kells AP, Forsayeth J, Bankiewicz KS. Glial-derived neurotrophic factor gene transfer for Parkinson's disease: anterograde distribution of AAV2 vectors in the primate brain. Neurobiol Dis 2012;48: 228-235.
12. Xiao PJ, Lentz TB, Samulski RJ. Recombinant adeno-associated virus: clinical application and development as a gene-therapy vector. Ther Deliv 2012;3: 835-856.
13. McCown TJ. Adeno-associated virus (AAV) vectors in the CNS. Curr Gene Ther 2011;11: 181-188.
14. Forsayeth J, Bankiewicz KS, Aminoff MJ. Gene therapy for Parkinson's disease: where are we now and where are we going? Exp Rev Neurother 2010;10: 1839-1845.
15. Federici T, Taub JS, Baum GR, et al. Robust spinal motor neuron transduction following intrathecal delivery of AAV9 in pigs. Gene Ther 2012;19: 852-859.
16. Gray SJ, Matagne V, Bachaboina L, et al. Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates. Mol Ther 2011;19: 1058-1069.
17. Samaranch L, Salegio EA, San Sebastian W, et al. Adeno-associated virus serotype 9 transduction in the central nervous system of nonhuman primates. Hum Gene Ther 2012;23: 382-389.
18. Ciesielska A, Mittermeyer G, Hadaczek P, et al. Anterograde axonal transport of AAV2-GDNF in rat basal ganglia. Mol Ther 2011;19: 922-927.
19. Kells AP, Hadaczek P, Yin D, et al. Efficient gene therapy-based method for the delivery of therapeutics to primate cortex. Proc Natl Acad Sci U S A 2009;106: 2407-2411.
20. 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 pro-drug approach. Exp Neurol 2000;164: 2-14.
21. Hadaczek P, Mirek H, Bringas J, et al. Basic fibroblast growth factor enhances transduction, distribution, and axonal transport of adeno-associated virus type 2 vector in rat brain. Hum Gene Ther 2004;15: 469-479.
22. Salegio EA, Samaranch L, Kells AP, et al. Axonal transport of adeno-associated viral vectors is serotype-dependent. Gene Ther 2013;20: 348-352.
23. Christine CW, Starr PA, Larson PS, et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 2009;73: 1662-1669.
24. 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.
25. Forsayeth JR, Bankiewicz KS. AAV9: over the fence and into the woods. Mol Ther 2011;19: 1006-1007.
26. Foust KD, Nurre E, Montgomery CL, et al. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol 2009;27: 59-65.
27. Pulicherla N, Shen S, Yadav S, et al. Engineering liver-detargeted AAV9 vectors for cardiac and musculoskeletal gene transfer. Mol Ther 2011;19: 1070-1078.
28. Towne C, Pertin M, Beggah AT, et al. Recombinant adeno-associated virus serotype 6 (rAAV2/6)-mediated gene transfer to nociceptive neurons through different routes of delivery. Mol Pain 2009;5: 52.
29. Jacques SJ, Ahmed Z, Forbes A, et al. AAV8(gfp) preferentially targets large diameter dorsal root ganglion neurones after both intra-dorsal root ganglion and intrathecal injection. Mol Cell Neurosci 2012;49: 464-474.
30. Xu Q, Chou B, Fitzsimmons B, et al. In vivo gene knockdown in rat dorsal root ganglia mediated by self-complementary adeno-associated virus serotype 5 following intrathecal delivery. PloS one 2012;7: e32581.
31. Vandenberghe LH, Wang L, Somanathan S, et al. Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid. Nat Med 2006;12: 967-971.
32. Mandel RJ, Burger C. Clinical trials in neurological disorders using AAV vectors: promises and challenges. Curr Opin Mol Ther 2004;6: 482-490.
33. Peden CS, Burger C, Muzyczka N, et al. 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 2004;78: 6344-6359.
34. Reimsnider S, Manfredsson FP, Muzyczka N, et al. Time course of transgene expression after intrastriatal pseudotyped rAAV2/1, rAAV2/2, rAAV2/5, and rAAV2/8 transduction in the rat. Mol Ther 2007;15: 1504-1511.
35. Forsayeth JR. Influence of the Immune system on central nervous system gene transfer. In: Kaplitt MG, During MJ (eds) Gene therapy of the central nervous system - from bench to bedside. Academic Press, Amsterdam; 2006: pp. 45-52.
36. Sanftner LM, Suzuki BM, Doroudchi MM, et al. Striatal delivery of rAAV-hAADC to rats with preexisting immunity to AAV. Mol Ther 2004;9: 403-409.
37. 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.
38. 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.
39. Madsen D, Cantwell ER, O'Brien T, et al. Adeno-associated virus serotype 2 induces cell-mediated immune responses directed against multiple epitopes of the capsid protein VP1. J Gen Virol 2009;90: 2622-2633.
40. Calcedo R, Morizono H, Wang L, et al. Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clin Vaccine Immunol 2011;18: 1586-1588.
41. Ciesielska A, Hadaczek P, Mittermeyer G, et al. Cerebral infusion of AAV9 vector-encoding non-self proteins can elicit cell-mediated immune responses. Mol Ther 2013;21: 158-166.
42. Hadaczek P, Forsayeth J, Mirek H, et al. Transduction of nonhuman primate brain with adeno-associated virus serotype 1: vector trafficking and immune response. Hum Gene Ther 2009;20: 225-237.
43. Gao G, Wang Q, Calcedo R, et al. Adeno-associated virus-mediated gene transfer to nonhuman primate liver can elicit destructive transgene-specific T cell responses. Hum Gene Ther 2009;20: 930-942.
44. Bartus RT, Herzog CD, Chu Y, et al. Bioactivity of AAV2-neurturin gene therapy (CERE-120): differences between Parkinson's disease and nonhuman primate brains. Mov Disord 2011;26: 27-36.
45. Eberling JL, Jagust WJ, Christine CW, et al. Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology 2008;70: 1980-1983.
46. Marks WJ, Jr., Bartus RT, Siffert J, et al. Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol 2010;9: 1164-1172.
47. Bobo R, Laske D, Akbasak A, et al. Convection-enhanced delivery of macromolecules in the brain. PNAS 1994;91: 2076-2080.
48. Hadaczek P, Yamashita Y, Mirek H, et al. The "perivascular pump" driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain. Mol Ther 2006;14: 69-78.
49. Richardson RM, Kells AP, Martin AJ, et al. Novel platform for MRI-guided convection-enhanced delivery of therapeutics: preclinical validation in nonhuman primate brain. Stereotact Funct Neurosurg 2011;89: 141-151.
50. Fiandaca MS, Varenika V, Eberling J, et al. Real-time MR imaging of adeno-associated viral vector delivery to the primate brain. Neuroimage 2009;47(Suppl. 2): T27-35.
51. Fiandaca M, Forsayeth J, Dickinson P, et al. Image-guided convection-enhanced delivery platform in the treatment of neurological diseases. Neurotherapeutics 2008;5: 123-127.
52. Richardson RM, Kells AP, Rosenbluth KH, et al. Interventional MRI-guided putaminal delivery of AAV2-GDNF for a planned clinical trial in Parkinson's disease. Mol Ther 2011;19: 1048-1057.
53. Su X, Kells AP, Aguilar Salegio E, et al. Real time MRI imaging with gadoteridol predicts distribution of transgenes after convection-enhanced delivery of AAV2 vectors. Mol Ther 2010;18: 1490-1495.
54. Lonser RR, Warren KE, Butman JA, et al. Real-time image-guided direct convective perfusion of intrinsic brainstem lesions. Technical note. J Neurosurg 2007;107: 190-197.
55. Krauze MT, Saito R, Noble C, et al. Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents. J Neurosurg 2005;103: 923-929.
56. Saito R, Krauze MT, Bringas JR, et al. Gadolinium-loaded liposomes allow for real-time magnetic resonance imaging of convection-enhanced delivery in the primate brain. Exp Neurol 2005;196: 381-389.
57. Yin D, Richardson RM, Fiandaca MS, et al. Cannula placement for effective convection-enhanced delivery in the nonhuman primate thalamus and brainstem: implications for clinical delivery of therapeutics. J Neurosurg 2010;113: 240-248.
58. Yin D, Valles FE, Fiandaca MS, et al. Optimal region of the putamen for image-guided convection-enhanced delivery of therapeutics in human and non-human primates. Neuroimage 2011;54(Suppl. 1): S196-203.
59. Braak H, Braak E, Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82: 239-259.
60. Kovacs T, Cairns NJ, Lantos PL. Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages. Neuroreport 2001;12: 285-288.
61. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992;256: 184-185.
62. Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010;362: 329-344.
63. Hardy J. The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. J Neurochem 2009;110: 1129-1134.
64. Tanzi RE, Bertram L. Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 2005;120: 545-555.
65. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 2001;81: 741-766.
66. Mawuenyega KG, Sigurdson W, Ovod V, et al. Decreased clearance of CNS beta-amyloid in Alzheimer's disease. Science 2010;330: 1774.
67. Weiner HL, Selkoe DJ. Inflammation and therapeutic vaccination in CNS diseases. Nature 2002;420: 879-884.
68. Morgan D. Immunotherapy for Alzheimer's disease. J Intern Med 2011;269: 54-63.
69. Birmingham K, Frantz S. Set back to Alzheimer vaccine studies. Nat Med 2002;8: 199-200.
70. Levites Y, Jansen K, Smithson LA, et al. Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice. J Neurosci 2006;26: 11923-11928.
71. Ryan DA, Mastrangelo MA, Narrow WC, et al. Abeta-directed single-chain antibody delivery via a serotype-1 AAV vector improves learning behavior and pathology in Alzheimer's disease mice. Mol Ther 2010;18: 1471-1481.
72. Liu Y, Studzinski C, Beckett T, et al. Expression of neprilysin in skeletal muscle reduces amyloid burden in a transgenic mouse model of Alzheimer disease. Mol Ther 2009;17: 1381-1386.
73. Kuo YM, Kokjohn TA, Beach TG, et al. Comparative analysis of amyloid-beta chemical structure and amyloid plaque morphology of transgenic mouse and Alzheimer's disease brains. J Biol Chem 2001;276: 12991-12998.
74. Richardson JA, Burns DK, Mouse models of Alzheimer's disease: a quest for plaques and tangles. ILAR J 2002;43: 89-99.
75. Farfara D, Lifshitz V, Frenkel D, Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease. J Cell Mol Med 2008;12: 762-780.
76. Kiyota T, Okuyama S, Swan RJ, et al. CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer's disease-like pathogenesis in APP+PS1 bigenic mice. FASEB J 2010;24: 3093-3102.
77. Kiyota T, Ingraham KL, Swan RJ, et al. AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice. Gene Ther 2012;19: 724-733.
78. Braak H, Del Tredici K, Rub U, et al. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003;24: 197-211.
79. Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008;79: 368-376.
80. Tan JM, Wong ES, Lim KL. Protein misfolding and aggregation in Parkinson's disease. Antioxid Redox Signal 2009;11: 2119-2134.
81. Dong Z, Wolfer DP, Lipp HP, et al. Hsp70 gene transfer by adeno-associated virus inhibits MPTP-induced nigrostriatal degeneration in the mouse model of Parkinson disease. Mol Ther 2005;11: 80-88.
82. Jung AE, Fitzsimons HL, Bland RJ, et al. HSP70 and constitutively active HSF1 mediate protection against CDCrel-1-mediated toxicity. Mol Ther 2008;16: 1048-1055.
83. Gao L, Diaz-Martin J, Dillmann WH, et al. Heat shock protein 70 kDa over-expression and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced nigrostriatal degeneration in mice. Neuroscience 2011;193: 323-329.
84. Chesselet MF. In vivo alpha-synuclein overexpression in rodents: a useful model of Parkinson's disease? Exp Neurol 2008;209: 22-27.
85. Kirik D, Rosenblad C, Burger C, et al. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 2002;22: 2780-2791.
86. Lo Bianco C, Ridet JL, Schneider BL, et al. alpha-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc Natl Acad Sci U S A 2002;99: 10813-10818.
87. Kirik D, Annett LE, Burger C, et al. Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson's disease. Proc Natl Acad Sci U S A 2003;100: 2884-2889.
88. Chu Y, Kordower JH. Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson's disease? Neurobiol Dis 2007;25: 134-149.
89. Sapru MK, Yates JW, Hogan S, et al. Silencing of human alpha-synuclein in vitro and in rat brain using lentiviral-mediated RNAi. Exp Neurol 2006;198: 382-390.
90. Khodr CE, Sapru MK, Pedapati J, et al. An alpha-synuclein AAV gene silencing vector ameliorates a behavioral deficit in a rat model of Parkinson's disease, but displays toxicity in dopamine neurons. Brain Res 2011;1395: 94-107.
91. Han Y, Khodr CE, Sapru MK, et al. A microRNA embedded AAV alpha-synuclein gene silencing vector for dopaminergic neurons. Brain Res 2011;1386: 15-24.
92. Fiandaca MS, Bankiewicz KS. Gene therapy for Parkinson's disease: from non-human primates to humans. Curr Opin Mol Ther 2010;12: 519-529.
93. 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.
94. LeWitt PA, Rezai AR, Leehey MA, et al. AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 2011;10: 309-319.
95. Valles F, Fiandaca MS, Eberling JL, et al. Qualitative imaging of adeno-associated virus serotype 2-human aromatic L-amino acid decarboxylase gene therapy in a phase I study for the treatment of Parkinson disease. Neurosurgery 2010;67: 1377-1385.
96. Gill SS, Patel NK, Hotton GR, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 2003;9: 589-595.
97. 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 2006;59: 459-466.
98. Patel NK, Gill SS. GDNF delivery for Parkinson's disease. Acta Neurochir Suppl 2007;97: 135-154.
99. Slevin JT, Gash DM, Smith CD, et al. Unilateral intraputamenal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year of treatment and 1 year of withdrawal. J Neurosurg 2007;106: 614-620.
100. Denyer R, Douglas MR. Gene therapy for Parkinson's disease. Parkinsons Dis 2012;2012: 757305.
101. San Sebastian W, Richardson RM, Kells AP, et al. Safety and tolerability of magnetic resonance imaging-guided convection-enhanced delivery of AAV2-hAADC with a novel delivery platform in nonhuman primate striatum. Hum Gene Ther 2012;23: 210-217.
102. Patel NK, Bunnage M, Plaha P, et al. Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: a two-year outcome study. Ann Neurol 2005; 57: 298-302.
103. Huddleston DE, Factor SA, Of monkeys and men: analysis of the phase 2 double-blind, sham-surgery controlled, randomized trial of AAV2-neurturin gene therapy for Parkinson's disease. Curr Neurol Neurosci Rep 2011;11: 345-348.
104. Kells AP, Eberling J, Su X, et al. Regeneration of the MPTP-lesioned dopaminergic system after convection-enhanced delivery of AAV2-GDNF. J Neurosci 2010;30: 9567-9577.
105. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 1993;72: 971-983.
106. Walker FO. Huntington's disease. Lancet 2007;369: 218-228.
107. DiFiglia M, Sapp E, Chase KO, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997;277: 1990-1993.
108. Ross CA, Tabrizi SJ, Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 2011;10: 83-98.
109. Yamamoto A, Lucas JJ, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 2000;101: 57-66.
110. Vagner T, Young D, Mouravlev A. Nucleic acid-based therapy approaches for huntington's disease. Neurol Res Int 2012;2012: 358370.
111. Sah DW, Aronin N. Oligonucleotide therapeutic approaches for Huntington disease. J Clin Invest 2011;121: 500-507.
112. 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 The, 2009;17: 1053-1063.
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 U S A 2007;104: 17204-17209.
114. Drouet V, Perrin V, Hassig R, et al. Sustained effects of nonallele-specific Huntingtin silencing. Ann Neurol 2009;65: 276-285.
115. 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 U S A 2005;102: 5820-5825.
116. Machida Y, Okada T, Kurosawa M, et al. rAAV-mediated shRNA ameliorated neuropathology in Huntington disease model mouse. Biochem Biophys Res Commun 2006;343: 190-197.
117. 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 U S A 2008;105: 5868-5873.
118. Rodriguez-Lebron E, Denovan-Wright EM, Nash K, et al. Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice. Mol Ther 2005;12: 618-633.
119. Dragatsis I, Levine MS, Zeitlin S. Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nat Genet 2000;26: 300-306.
120. McBride JL, Pitzer MR, Boudreau RL, et al. Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington's disease. Mol Ther 2011;19: 2152-2162.
121. Gagnon KT, Pendergraff HM, Deleavey GF, et al. Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat. Biochemistry 2010;49: 10166-10178.
122. Hu J, Matsui M, Gagnon KT, et al. Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs. Nat Biotechnol 2009;27: 478-484.
123. Carroll JB, Warby SC, Southwell AL, et al. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin. Mol Ther 2011;19: 2178-2185.
124. Liu W, Kennington LA, Rosas HD, et al. Linking SNPs to CAG repeat length in Huntington's disease patients. Nat Methods 2008;5: 951-953.
125. Pfister EL, Kennington L, Straubhaar J, et al. Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients. Curr Biol 2009;19: 774-778.
126. Bennett CF, Swayze EE. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 2010;50: 259-293.
127. Kordasiewicz HB, Stanek LM, Wancewicz EV, et al. Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron 2012;74: 1031-1044.
128. Stiles DK, Zhang Z, Ge P, et al. Widespread suppression of huntingtin with convection-enhanced delivery of siRNA. Exp Neurol 2012;233: 463-471.
129. Miller RG, Gelinas D, O'Connor P. Amyotrophic lateral sclerosis. American Academy of Neurology Press, New York; 2005.
130. Kaspar BK, Frost LM, Christian L, et al. Synergy of insulin-like growth factor-1 and exercise in amyotrophic lateral sclerosis. Ann Neurol 2005;57: 649-655.
131. Mello CC, Conte D, Jr. Revealing the world of RNA interference. Nature 2004;431: 338-342.
132. 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 2005;11: 423-428.
133. 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 2005;11: 429-433.
134. Winer L, Srinivasan D, Chun S, et al. SOD1 in cerebral spinal fluid as a pharmacodynamic marker for antisense oligonucleotide therapy. JAMA Neurol 2013;70: 201-207.
135. Kubodera T, Yamada H, Anzai M, et al. In vivo application of an RNAi strategy for the selective suppression of a mutant allele. Hum Gene Ther 2011;22: 27-34.
136. Berry JD, Cudkowicz ME. New considerations in the design of clinical trials for amyotrophic lateral sclerosis. Clin Invest 2011;1: 1375-1389.
137. Kitamoto T, Tateishi J, Tashima T, et al. Amyloid plaques in Creutzfeldt-Jakob disease stain with prion protein antibodies. Ann Neurol 1986;20: 204-208.
138. Cohen FE, Pan KM, Huang Z, et al. Structural clues to prion replication. Science 1994;264: 530-531.
139. Goldfarb LG, Brown P, Haltia M, et al. Creutzfeldt-Jakob disease cosegregates with the codon 178Asn PRNP mutation in families of European origin. Ann Neurol 1992;31: 274-281.
140. Prusiner SB. Molecular biology of prion diseases. Science 1991;252: 1515-1522.
141. Enari M, Flechsig E, Weissmann C. Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proc Natl Acad Sci U S A 2001;98: 9295-9299.
142. Feraudet C, Morel N, Simon S, et al. Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells. J Biol Chem 2005;280: 11247-11258.
143. Perrier V, Solassol J, Crozet C, et al. Anti-PrP antibodies block PrPSc replication in prion-infected cell cultures by accelerating PrPC degradation. J Neurochem 2004;89: 454-463.
144. White AR, Enever P, Tayebi M, et al. Monoclonal antibodies inhibit prion replication and delay the development of prion disease. Nature 2003;422: 80-83.
145. Wuertzer CA, Sullivan MA, Qiu X, et al. CNS delivery of vectored prion-specific single-chain antibodies delays disease onset. Mol Ther 2008;16: 481-486.
146. Padiolleau-Lefevre S, Alexandrenne C, Dkhissi F, et al. Expression and detection strategies for an scFv fragment retaining the same high affinity than Fab and whole antibody: Implications for therapeutic use in prion diseases. Mol Immunol 2007;44: 1888-1896.
147. Mallucci GR, Ratte S, Asante EA, et al. Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration. EMBO J 2002;21: 202-210.
148. Mallucci G, Dickinson A, Linehan J, et al. Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 2003;302: 871-874.
149. White MD, Farmer M, Mirabile I, et al. Single treatment with RNAi against prion protein rescues early neuronal dysfunction and prolongs survival in mice with prion disease. Proc Natl Acad Sci U S A 2008;105: 10238-10243.
150. Verity NC, Mallucci GR. Rescuing neurons in prion disease. Biochem J 2011;433: 19-29.
151. Stieger K, Belbellaa B, Le Guiner C, et al. In vivo gene regulation using tetracycline-regulatable systems. Adv Drug Deliv Rev 2009;61: 527-541.
152. Goverdhana S, Puntel M, Xiong W, et al. Regulatable gene expression systems for gene therapy applications: progress and future challenges. Mol Ther 2006; 12: 189-211.