Trophic Factor Gene Therapy for Parkinson's Disease

Movement Disorders

Volumn 28, Issue 1, 2013, Pages 96-109

  Kordower, Jeffrey H ^a   Bjorklund, Anders ^b  

^a RUSH UNIVERSITY MEDICAL CENTER   (United States)

^b LUND UNIVERSITY   (Sweden)

Author keywords

GDNF; Neuroprotection; Neurturin; Parkinson's disease; Regeneration

Indexed keywords

ADENOVIRUS VECTOR; CERE 120; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; LENTIVIRUS VECTOR; LIATERMIN; NEURTURIN; PARVOVIRUS VECTOR; PLACEBO; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG;

ANOREXIA; DEPRESSION; DOPAMINERGIC NERVE CELL; DOPAMINERGIC SYSTEM; DOSE RESPONSE; DRUG CAPSULE; DRUG EFFICACY; EX VIVO GENE TRANSFER; GENE DELIVERY SYSTEM; GENE EXPRESSION; GENE TARGETING; GENE THERAPY; GENETIC ENGINEERING; HUMAN; IMMUNOREACTIVITY; INFUSION; MOTOR DYSFUNCTION; NAUSEA; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; VIRAL GENE DELIVERY SYSTEM; VOMITING; WEIGHT REDUCTION;

GENE TRANSFER TECHNIQUES; GENETIC THERAPY; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; PARKINSON DISEASE;

EID: 84873445906     PISSN: 08853185     EISSN: 15318257     Source Type: Journal    
DOI: 10.1002/mds.25344     Document Type: Review

References (85)

1. Hughes PE, Alexi T, Walton M, et al. Activity and injury-dependent expression of inducible trophic factors, growth factors, and apoptosis-related genes within the central nervous system. Prog Neurobiol 1999;57:421-450.
2. Mattson MP. Neuroprotective strategies based on targeting of post-receptor signaling events. In: Neuroprotective Signal Transduction. Totowa, NJ: Humana Press; 1998:301-335.
3. Lin LF, Doherty DH, Lile JD, et al. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993;260:1130-1132.
4. Meyer M, Johansen J, Gramsbergen JB, et al. Improved survival of embryonic porcine dopaminergic neurons in coculture with a conditionally immortalized GDNF-producing hippocampal cell line. Exp Neurol 2000;164:82-93.
5. Clarkson ED, Zawada WM, Freed CR. GDNF improves survival and reduces apoptosis in human embryonic dopaminergic neurons in vitro. Cell Tissue Res 1997;289:207-210.
6. Hou GJ, Lin LH, Mytilineou C. Glial cell line derived neurotrophic factor exerts neurotrophic effects on dopaminergic neurons in vitro and promotes their survival and regrowth after damage by 1-methyl-4-phenylpyridinium. J Neurochem 1996;66:74-82.
7. Eggert K, Schlegel J, Oertel W, Würz C, Krieg JC, Vedder H. Glial cell line-derived neurotrophic factor protects dopaminergic neurons from 6-hydroxydopamine toxicity in vitro. Neurosci Lett 1999;269:178-182.
8. 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 1994;182:107-111.
9. Beck KD, Valverde J, Alexi T, Poulsen K, et al. Mesencephalic dopamine neurons protected by GDNF from axotomy-induced degeneration in adult brain. Nature 1995;335:479-489.
10. Bowenkamp KE, Hoffman AF, Gerhardt GA, et al. Glial cell line derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons. J Comp Neurol 1995;355:479-489.
11. Winkler C, Sauer H, Lee C, et al. A. Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's disease. J Neurosci 1996;16:7206-7215.
12. Kirik D, Rosenblad C, Bjorklund A. Preservations of a functional nigrostriatal dopamine pathway by GDNF in the intrastriatal 6-OHDA lesion model depend on the site of administration of the trophic factor. Eur J Neurosci 2000;12:3871-3882.
13. Kordower JH, Palfi S, Chen EY, et al. Clinicopathological findings following intraventricular glial cell line-derived neurotrophic factor treatment in a patient with Parkinson's disease. Ann Neurol 1999;46:419-424.
14. Gash DM, Zhang Z, Cass WA, et al. Morphological and functional effects of intranigrally administered GDNF in normal rhesus monkeys. J Comp Neurol 1995;363:345-358.
15. Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996;380:252-255.
16. Miyoshi Y, Zhang Z, Ovadia A, et al. Glial cell line-derived neurotrophic factor-levodopa interactions and reduction of side effects in parkinsonian monkeys. Ann Neurol 1997;42:208-214.
17. Salvatore MF, Ai Y, Fischer B, Zhang AM, et al. Point source concentration of GDNF may explain failure of phase II clinical trial. Exp Neurol 2006;202:497-505.
18. Nutt JG, Burchiel KJ, Comella CL, Jankovic J, et al.; ICV GDNF Study Group. Implanted intracerebroventricular. Glial cell line-derived neurotrophic factor. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 2003;60:69-73.
19. Gill SS, Patel NK, Hotton GR, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson's disease. Nat Med 2003;9:589-595.
20. Slevin JT, Gerhardt GA, Smith CD, et al. Improvement of bilateral motor functions in patients with Parkinson's disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg 2005;102:216-222.
21. Amgen Incorporated. Amgen's phase 2 study of GDNF for advanced Parkinson's disease fails to meet primary endpoint; six months of treatment showed biological effect but no clinical improvement. June 28, 2004. Available at: http://www.amgen.com/media/media_pr_detail.jsp?year=&releaseID=585632. Accessed December 16, 2012.
22. Sherer TB, Fiske BK, Svendsen CN, et al. Crossroads in GDNF therapy for Parkinson's disease. Mov Disord 2006;21:136-141.
23. Slevin JT, Gash DM, Smith CD, et al. Unilateral intraputamenal glial cell line-derived neurotrophic factor in patients with Parkinson's disease: response to 1 year of treatment and 1 year of withdrawal. J Neurosurg 2007;106:614-620.
24. 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.
25. Fisher LJ, Jinnah HA, Kale LC, et al. Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-dopa. Neuron 1991;6:371-380.
26. Fitoussi N, Sotnik-Barkai I, Tomatore C, et al. Dopamine turnover and metabolism in the striatum of parkinsonian rats grafted with genetically-modified human astrocytes. Neuroscience 1998;85:405-413.
27. Wolfe J, Fisher L, Xu L, et al. Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson's disease. Proc Natl Acad Sci USA 1989;86:9011-9014.
28. Lundberg C, Horellou P, Mallet J, et al. Generation of dopa producing astrocytes by retroviral transduction of the human tyrosine hydroxylase gene-in vitro characterization and in vivo effects in the rat Parkinson model. Exp Neurol 1996;139:39-53.
29. Lindvall O, Wahlberg LU, Encapsulated biocell delivery of GDNF: a novel clinical strategy for neuroprotection an neuroregeneration in Parkinsons's disease? Exp Neurol 2008;209:82-88.
30. Tseng JL, Baetge EE, Zurn AD, et al. GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine. J Neurosci 1997;17:325-333.
31. Sajadi A, Bensadoun JC, Schneider BL, et al. Transient striatal delivery of GDNF via encapsulated cells leads to sustained behavioral improvement in a bilateral model of Parkinson disease. Neurobiol Dis 2006;22:119-129.
32. Akerud P, Canals JM, Snyder EY, et al. Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in mouse model of Parkinson's disease. J Neurosci 2001;21:8108-8118.
33. Annett LE, Martel FL, Rogers DC, et al. Behavioral assessment of the effects of embryonic nigral grafts in marmosets with unilateral 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 1994;125:228-246.
34. Behrstock S, Ebert A, McHugh J, et al. Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates. Gene Ther 2006;13:379-388.
35. Cunningham LA, Su C. Astrocyte delivery of glial cell line-derived neurotrophic factor in a mouse model of Parkinson's disease. Exp Neurol 2002;174:230-242.
36. Bjorklund A, Kirik D, Rosenblad C, et al. Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res 2000;886:82-98.
37. Choi-Lundberg DL, Lin Q, Chang YN, et al. Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 1997;275:838-841.
38. Kojima H, Abiru Y, Sakajira K, et al. Adenovirus mediated transduction with human glial cell line-derived neurotrophic factors gene prevents 1-methyl-4-phenyl, 1, 2, 3, 6-tetrahydro-pyridine-induced dopamine depletion in striatum of mouse brain. Biochem Biophys Res Commun 1997;238:569-573.
39. Yang Y, Nunes FA, Berencsi K, et al. Cellular immunity to viral antigens limits E1-delected adenoviruses for gene therapy. Proc Natl Acad Sci U S A 1994;91:4407-4411.
40. Dai Y, Schwarz EM, Gu, D, et al. Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: tolerization of factor IX and vector antigens allows for long-term expression. Proc Natl Acad Sci U S A 1995;92:1401-1405.
41. Zhou H, O'Neal W, Morran N, et al Development of a complementing cell line and a system for construction of adenovirus vectors with E1 and E2a deleted. J Virol 1996;70:7030-7038.
42. Armentano D, Smith MP, Sookdeo CC, et al. E4ORF3 requirement for achieving long-term transgene expression from the cytomegalovirus promoter in adenovirus vectors. J Virol 1999;73:7031-7034.
43. Ilan Y, Droguett G, Chowdhury NR et al. Insertion of the andenoviral E3 region into a recombinant viral vector prevents antiviral humoral and cellular immune responses and permits long-term gene expression. Proc Natl Acad Sci U S A 1997;94:2587-2592.
44. Do Thi NA, Saillour P, Ferrero L, et al. Delivery of GDNF by an E1, E3/E4 deleted adenoviral vector and driven by a GFAP promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson's disease. Gene Ther 2004;11:746-756.
45. Do Thi NA, Saillour P, Ferrero L, Paunio T, Mallet J. Does neuronal expression of GDNF effectively protect dopaminergic neurons in a rat model of Parkinson's disease? Gene Ther 2007;14:441-450.
46. Wu Z, Asokan A, Samulski RJ. Adenoassociated virus serotypes: vector toolkit for human gene therapy. Mol Ther 2006;14:316-327.
47. Herzog RW. Immune responses to AAV capsid: are mice not humans after all? Mol Ther 2007;15:649-650.
48. Mandel RJ, Spratt SK, Snyder RO, et al. Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson's disease in rats. Proc Natl Acad U S A 1997;94:14083-14088.
49. Kirik D, Rosenblad C, Bjorklund A, et al. 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 2000;20:4686-4700.
50. Wang L, Muramatsu S, Lu Y, et al. Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease. Gene Ther 2002;9:381-389.
51. Eslamboli A, Cummings RM, Ridley R.M, 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.
52. Eberling JL, Kens AP, Pivirotto P, et al. Functional effects of AAV2-GDNF on the dopaminergic nigrostriatal pathway in parkinsonian rhesus monkeys. Hum Gene. Ther 2009;20:511-518.
53. Johnston LC, Eberling J, Piviroto P, et al. Clinically relevant effects of AAV2-GDNF on the dopaminergic nigrostriatal pathway in aged rhesus monkeys. Hum Gene Ther 2009;20:497-510.
54. Déglon 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 2000;11:179-190.
55. Bensadoun JC, Déglon N, Tseng JL, et al. Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson's disease using GDNF. Exp Neurol 2000;164:15-24.
56. Georgievska B, Kirik D, Rosenblad C, et al. Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector. Neuroreport 2002;13:75-82.
57. Kordower JH, Bloch J, Ma SY, et al. Lentiviral gene transfer to the nonhuman primate brain. Exp Neurol 1999;160:1-16.
58. Kordower JH, Emborg ME, Bloch J, et al. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 2000;290:767-773.
59. Emborg ME, Ma SY, Mufson EJ, et al. Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys. J Comp Neurol 1998;401:253-265.
60. LoBianco BC, Ridet JL, Schneider BL, et al. α-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.
61. LoBianco BC, Deglon N, Pralong W, et al. Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease. Neurobiol Dis 2004;17:283-289.
62. Decressac M, Ulusoy A, Mattsson B, et al. GDNF fails to exert neuroprotection in a rat α-synuclein model of Parkinson's disease. Brain 2011;134:2302-2311.
63. Decressac M, Kadkhodaei B. Mattsson B, Laguna A, Perlmann T, Björklund A. a-Synuclein-Induced Down-Regulation of Nurr1 Disrupts GDNF Signaling in Nigral Dopamine Neurons Sci Transl Med 2012;5:156-163.
64. 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.
65. Kotzbauer PT, Lampe P, Heuckeroth RO, et al. Neurturin, a relative of glial-cell-line derived neurotrophic factor. Nature 1996;384:467-470.
66. Creedon DJ, Tansey MG, Baloh RH, et al. Neurturin shares receptors and signal transduction pathways with glial cell line-derived neurotrophic factor in sympathetic neurons. Proc Natl Acad Sci U S A 1997;94:7018-7023.
67. Ye M, Wang XJ, Zhang YH, et al. Transplantation of bone marrow stromal cells containing the neurturin gene in rat model of Parkinson's disease. Brain Res 2007;1142:206-216.
68. Liu WG, Lu GQ, Li B, Chen SD. Dopaminergic neuroprotection by neurturin-expressing c17.2 neural stem cells in a rat model of Parkinson's disease. Parkinsonism Relat Disord 2007;13:77-88.
69. 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 1999;11:1554-1566.
70. Oiwa Y, Yoshimura R, Nakai K, et al. Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral, biochemical and histochemical measurements in a model of Parkinson's disease. Brain Res 2002;947:271-283.
71. Grondin R, Zhang Z, Ai Y, et al. Intraputaminal infusion of exogenous neurturin protein restores motor and dopaminergic function in the globus pallidus of MPTP-lesioned rhesus monkeys. Cell Transplant 2008;17:373-381.
72. Fjord-Larsen L, Johansen JL, Kusk P, et al. a modified Neurturin construct. Exp Neurol 2005;195:49-60.
73. Bartus RT, Herzog CD, Bishop K, et al. Issues regarding gene therapy products for Parkinson's disease: the development of CERE-120 (AAV-NTRN) as one reference point. Parkinsonism Related Disord 2007;13(Suppl 3):S469-S477.
74. Gasmi M, Herzog CD, Brandon EP, et al. Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neuron degeneration in Parkinson's disease. Mol Ther 2007;15:62-68.
75. Gasmi M, Brandon EP, Herzog CD, et al. 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 2007;27:67-76.
76. Herzog CD, Dass B, Gasmi M, et al. Transgene expression, bioactivity, and safety of CERE-120 (AAV-Neurturin) following delivery to the monkey striatum. Mol Ther 2008;16:1737-1744.
77. 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.
78. Bjorklund A, Rosenblad C, Windler C, et al. Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson's disease. Neurobiol Dis 1997;4:186-200.
79. Kirik D, Georgievska B, Bjorklund A. Localized delivery of GDNF as a treatment for Parkinson's disease. Nat Neurosci 2004;7:105-110.
80. Mufson EJ, Kroin JS, Sendera TJ, et al. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases. Prog Neurobiol 1999;57:451-484.
81. Lindsay RM, Wiegand SJ, Altar CA, et al Neurotrophic factors: from molecule to man. Trends Neurosci 1994;17:182-190.
82. Su X, Kells AP, Huang EJ, et al. Safety evaluation of AAV2-GDNF gene transfer into the dopaminergic nigrostriatal pathway in aged and parkinsonian rhesus monkeys. Hum Gene Ther 2009;20:1627-1640.
83. Roy S, Zhang B, Lee VM, et al. Axonal transport defects: a common theme in neurodegenerative diseases. Acta Neuropathol 2005;109:5-13.
84. De Vos KJ, Grierson AJ, Ackerley S, et al. Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci 2008;31:151-173.
85. Chu Y, Morfini GA, Langhamer LB, et al., Alterations in axonal transport motor proteins in sporadic and experimental Parkinson's disease. Brain 2012;135:2058-2073.