Prospects of Neurotrophic Factors for Parkinson's Disease: Comparison of Protein and Gene Therapy

Human Gene Therapy

Volumn 26, Issue 8, 2015, Pages 550-559

  Domanskyi, Andrii ^a   Saarma, Mart ^a   Airavaara, Mikko ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIPARKINSON AGENT; CEREBRAL DOPAMINE NEUROTROPHIC FACTOR; DOPAMINE; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; MESENCEPHALIC ASTROCYTE DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIC FACTOR; NEURTURIN; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG; VIRUS VECTOR; NERVE GROWTH FACTOR;

COMPARATIVE EFFECTIVENESS; DOPAMINE UPTAKE; DRUG EFFICACY; EVIDENCE BASED PRACTICE; GENE THERAPY; HUMAN; NONHUMAN; PARKINSON DISEASE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHENOTYPE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; VIRAL GENE DELIVERY SYSTEM; ANIMAL; CLINICAL TRIAL (TOPIC); COMPARATIVE STUDY; DOPAMINERGIC NERVE CELL; GENE VECTOR; GENETICS; LENTIVIRINAE; PATHOLOGY; PHYSIOLOGY;

ANIMALIA;

ANIMALS; CLINICAL TRIALS AS TOPIC; DOPAMINERGIC NEURONS; GENETIC THERAPY; GENETIC VECTORS; HUMANS; LENTIVIRUS; NERVE GROWTH FACTORS; PARKINSON DISEASE;

EID: 84939793372     PISSN: 10430342     EISSN: 15577422     Source Type: Journal    
DOI: 10.1089/hum.2015.065     Document Type: Review

References (111)

1. Weintraub D, and Burn DJ. Parkinson's disease: the quintessential neuropsychiatric disorder. Mov Disord 2011;26:1022-1031.
2. Halliday G, Lees A, and Stern M. Milestones in Parkinson's disease-clinical and pathologic features. Mov Disord 2011;26:1015-1021.
3. Bartels AL, and Leenders KL. Parkinson's disease: the syndrome, the pathogenesis and pathophysiology. Cortex 2009;45:915-921.
4. Moore DJ, West AB, Dawson VL, et al. Molecular pathophysiology of Parkinson's disease. Annu Rev Neurosci 2005;28:57-87.
5. Liss B, and Roeper J. Individual dopamine midbrain neurons: functional diversity and flexibility in health and disease. Brain Res Rev 2008;58: 314-321.
6. Bjorklund A, and Dunnett SB. Dopamine neuron systems in the brain: an update. Trends Neurosci 2007;30:194-202.
7. Online Mendelian Inheritance in Man (OMIM). Parkinson disease, late-onset; PD [entry 168600]. Johns Hopkins University, Baltimore, MD, 2015. Available from: http://omim.org/entry/168600
8. Nalls MA, Pankratz N, Lill CM, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat Genet 2014;46:989-993.
9. Gasser T, Hardy J, and Mizuno Y. Milestones in PD genetics. Mov Disord 2011;26:1042-1048.
10. Valente EM, Arena G, Torosantucci L, et al. Molecular pathways in sporadic PD. Parkinsonism Relat Disord 2012;18(Suppl 1):S71-S73.
11. Obeso JA, Rodriguez-Oroz MC, Goetz CG, et al. Missing pieces in the Parkinson's disease puzzle. Nat Med 2010;16:653-661.
12. Hirsch EC, and Hunot S. Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 2009;8:382-397.
13. Thomas B, and Beal MF. Parkinson's disease. Hum Mol Genet 2007;16(Spec No. 2): R183-R194.
14. Mosharov EV, Larsen KE, Kanter E, et al. Interplay between cytosolic dopamine, calcium, and a-synuclein causes selective death of substantia nigra neurons. Neuron 2009;62:218-229.
15. Liss B, Haeckel O, Wildmann J, et al. K-ATP channels promote the differential degeneration of dopaminergic midbrain neurons. Nat Neurosci 2005;8:1742-1751.
16. Guzman JN, Sanchez-Padilla J, Wokosin D, et al. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature 2010;468:696-700.
17. Nedergaard S, Flatman JA, and Engberg I. Nifedipine-and x-conotoxin-sensitive Ca2 + conductances in guinea-pig substantia nigra pars compacta neurones. J Physiol 1993;466:727-747.
18. Chan CS, Guzman JN, Ilijic E, et al. 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature 2007;447:1081-1086.
19. Meissner WG, Frasier M, Gasser T, et al. Priorities in Parkinson's disease research. Nat Rev Drug Discov 2011;10:377-393.
20. Bernheimer H, Birkmayer W, Hornykiewicz O, et al. Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J Neurol Sci 1973;20:415-455.
21. Scherman D, Desnos C, Darchen F, et al. Striatal dopamine deficiency in Parkinson's disease: role of aging. Ann Neurol 1989;26:551-557.
22. Kish SJ, Shannak K, and Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease: pathophysiologic and clinical implications. N Engl J Med 1988;318:876-880.
23. Airavaara M, Harvey BK, Voutilainen MH, et al. CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice. Cell Transplant 2012;21:1213-1223.
24. Schober A. Classic toxin-induced animal models of Parkinson's disease: 6-OHDA and MPTP. Cell Tissue Res 2004;318:215-224.
25. Rieker C, Engblom D, Kreiner G, et al. Nucleolar disruption in dopaminergic neurons leads to oxidative damage and parkinsonism through repression of mammalian target of rapamycin signaling. J Neurosci 2011;31:453-460.
26. Domanskyi A, Alter H, Vogt MA, et al. Transcription factors Foxa1 and Foxa2 are required for adult dopamine neurons maintenance. Front Cell Neurosci 2014;8:275.
27. Li Y, Liu W, Oo TF, et al. Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat Neurosci 2009; 12:826-828.
28. Ekstrand MI, Terzioglu M, Galter D, et al. Progressive parkinsonism in mice with respiratorychain-deficient dopamine neurons. Proc Natl Acad Sci U S A 2007;104:1325-1330.
29. Harvey BK, Richie CT, Hoffer BJ, et al. Transgenic animal models of neurodegeneration based on human genetic studies. J Neural Transm 2011;118:27-45.
30. Janezic S, Threlfell S, Dodson PD, et al. Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model. Proc Natl Acad Sci U S A 2013;110:E4016-E4025.
31. Ryan BJ, Hoek S, Fon EA, et al. Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem Sci 2015;40:200-210.
32. Leenders KL, Salmon EP, Tyrrell P, et al. The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson's disease. Arch Neurol 1990;47:1290-1298.
33. Cheng HC, Ulane CM, and Burke RE. Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol 2010;67:715-725.
34. Hagg T, Manthorpe M, Vahlsing HL, et al. Delayed treatment with nerve growth factor reverses the apparent loss of cholinergic neurons after acute brain damage. Exp Neurol 1988;101: 303-312.
35. Williams LR. Basal forebrain cholinergic lesions and complete transection of septal-hippocampal pathway. In: Paradigms of Neural Injury. JR Perez-Polo, ed. Academic Press, San Diego, CA. 1996; pp. 106-114.
36. Cheng HC, Kim SR, Oo TF, et al. Akt suppresses retrograde degeneration of dopaminergic axons by inhibition of macroautophagy. J Neurosci 2011; 31:2125-2135.
37. Ahtila S, Kaakkola S, Gordin A, et al. Effect of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled-release levodopacarbidopa in volunteers. Clin Neuropharmacol 1995;18:46-57.
38. Carlsson A, Lindqvist M, and Magnusson T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 1957;180:1200.
39. Cotzias GC. l-Dopa for Parkinsonism. N Engl J Med 1968;278:630.
40. Han F, Wang W, Chen B, et al. Human induced pluripotent stem cell-derived neurons improve motor asymmetry in a 6-hydroxydopamineinduced rat model of Parkinson's disease. Cytotherapy 2015;17:665-679.
41. Kordower JH, Chu Y, Hauser RA, et al. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 2008;14:504-506.
42. Li JY, Englund E, Holton JL, et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 2008;14:501-503.
43. Mendez I, Vinuela A, Astradsson A, et al. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nat Med 2008;14:507-509.
44. Cave JW, Wang M, and Baker H. Adult subventricular zone neural stem cells as a potential source of dopaminergic replacement neurons. Front Neurosci 2014;8:16.
45. Saarma M, Karelson M, Bespalov M, Pilv M; GeneCode AS. Patent: Methods of facilitating neural cell survival using GDNF family ligand (GFL) mimetics or RET signaling pathway acti-vators. Publication No. QO/2011/070177. Publication Date 16 June 2011 [accessed 21 July 2015]. Available at: https://patentscope.wipo .int/search/en/detail.jsf?docId=WO2011070177 &recNum=1&maxRec=&office=&prevFilter=&sortOption=&queryString=&tab=PCT + Biblio
46. Weinreb O, Amit T, Bar-Am O, et al. Induction of neurotrophic factors GDNF and BDNF associated with the mechanism of neurorescue action of rasagiline and ladostigil: new insights and implications for therapy. Ann N Y Acad Sci 2007; 1122:155-168.
47. Airavaara M, Voutilainen MH, Wang Y, et al. Neurorestoration. Parkinsonism Relat Disord 2012; 18(Suppl 1):S143-S146.
48. Lindholm P, Voutilainen MH, Lauren J, et al. Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature 2007;448:73-77.
49. Petrova P, Raibekas A, Pevsner J, et al. MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons. J Mol Neurosci 2003;20:173-188.
50. Lindholm P, Peranen J, Andressoo JO, et al. MANF is widely expressed in mammalian tissues and differently regulated after ischemic and epileptic insults in rodent brain. Mol Cell Neurosci 2008;39:356-371.
51. Airaksinen MS, and Saarma M. The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci 2002;3:383-394.
52. Bespalov MM, Sidorova YA, Tumova S, et al. Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin. J Cell Biol 2011;192:153-169.
53. Paratcha G, Ledda F, and Ibanez CF. The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 2003;113:867-879.
54. 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.
55. Kotzbauer PT, Lampe PA, Heuckeroth RO, et al. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 1996;384:467-470.
56. Kearns CM, and Gash DM. GDNF protects nigral dopamine neurons against 6-hydroxydopamine in vivo. Brain Res 1995;672:104-111.
57. 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.
58. Sauer H, Rosenblad C, and Bjorklund A. Glial cell line-derived neurotrophic factor but not transforming growth factor b3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion. Proc Natl Acad Sci U S A 1995;92:8935-8939.
59. Voutilainen MH, Back S, Porsti E, et al. Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson's disease. J Neurosci 2009;29:9651-9659.
60. 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 progressive Parkinson's disease. Brain Res 2002;947:271-283.
61. Horger BA, Nishimura MC, Armanini MP, et al. Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J Neurosci 1998;18:4929-4937.
62. Hellman M, Arumae U, Yu LY, et al. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has a unique mechanism to rescue apoptotic neurons. J Biol Chem 2011;286:2675-2680.
63. Glembotski CC, Thuerauf DJ, Huang C, et al. Mesencephalic astrocyte-derived neurotrophic factor protects the heart from ischemic damage and is selectively secreted upon sarco/endoplasmic reticulum calcium depletion. J Biol Chem 2012;287: 25893-25904.
64. Henderson MJ, Richie CT, Airavaara M, et al. Mesencephalic astrocyte-derived neurotrophic factor (MANF) secretion and cell surface binding are modulated by KDEL receptors. J Biol Chem 2013;288:4209-4225.
65. Lindahl M, Danilova T, Palm E, et al. MANF is indispensable for the proliferation and survival of pancreatic beta cells. Cell Rep 2014;7:366-375.
66. Lindholm P, and Saarma M. Novel CDNF/MANF family of neurotrophic factors. Dev Neurobiol 2010;70:360-371.
67. Leader B, Baca QJ, and Golan DE. Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discov 2008;7: 21-39.
68. Parkash V, Leppanen VM, Virtanen H, et al. The structure of the glial cell line-derived neurotrophic factor-coreceptor complex: insights into RET signaling and heparin binding. J Biol Chem 2008;283:35164-35172.
69. Hamilton JF, Morrison PF, Chen MY, et al. Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin. Exp Neurol 2001;168:155-161.
70. 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.
71. Piccinini E, Kalkkinen N, Saarma M, et al. Glial cell line-derived neurotrophic factor: characterization of mammalian posttranslational modifications. Ann Med 2013;45:66-73.
72. Gash DM, Zhang Z, Ai Y, et al. Trophic factor distribution predicts functional recovery in parkinsonian monkeys. Ann Neurol 2005;58:224-233.
73. Lang AE, Gill S, Patel NK, et al. Randomized controlled trial of intraputamenal glial cell linederived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006;59:459-466.
74. 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.
75. Love S, Plaha P, Patel NK, et al. Glial cell linederived neurotrophic factor induces neuronal sprouting in human brain. Nat Med 2005;11: 703-704.
76. Slevin JT, Gerhardt GA, Smith CD, et al. Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg 2005; 102:216-222.
77. Howarth JL, Lee YB, and Uney JB. Using viral vectors as gene transfer tools. Cell Biol Toxicol 2010;26:1-20.
78. Karra D, and Dahm R. Transfection techniques for neuronal cells. J Neurosci 2010;30:6171-6177.
79. Bartus RT, Baumann TL, Brown L, et al. Advancing neurotrophic factors as treatments for agerelated neurodegenerative diseases: developing and demonstrating ''clinical proof-of-concept'' for AAV-neurturin (CERE-120) in Parkinson's disease. Neurobiol Aging 2013;34:35-61.
80. LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN 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.
81. Lim ST, Airavaara M, and Harvey BK. Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS. Pharmacol Res 2010;61:14-26.
82. Aschauer DF, Kreuz S, and Rumpel S. Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain. PLoS One 2013;8:e76310.
83. 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 2010;18: 588-593.
84. Barker RA, and Widner H. Immune problems in central nervous system cell therapy. NeuroRx 2004;1:472-481.
85. 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.
86. Mingozzi F, and High KA. Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood 2013;122:23-36.
87. Choi-Lundberg DL, Lin Q, Chang YN, et al. Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 1997;275: 838-841.
88. Kirik D, Rosenblad C, Bjorklund A, et al. Longterm 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.
89. McGrath J, Lintz E, Hoffer BJ, et al. Adenoassociated viral delivery of GDNF promotes recovery of dopaminergic phenotype following a unilateral 6-hydroxydopamine lesion. Cell Transplant 2002;11:215-227.
90. Kugler S, Lingor P, Scholl U, et al. Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control units. Virology 2003;311: 89-95.
91. Shevtsova Z, Malik JM, Michel U, et al. Promoters and serotypes: targeting of adenoassociated virus vectors for gene transfer in the rat central nervous system in vitro and in vivo. Exp Physiol 2005;90:53-59.
92. Cordero-Llana O, Houghton BC, Rinaldi F, et al. Enhanced efficacy of the CDNF/MANF family by combined intranigral overexpression in the 6-OHDA rat model of Parkinson's disease. Mol Ther 2015;23:244-254.
93. Ren X, Zhang T, Gong X, et al. AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model. Exp Neurol 2013;248:148-156.
94. Back S, Peranen J, Galli E, et al. Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease. Brain Behav 2013;3:75-88.
95. Arvidsson A, Kirik D, Lundberg C, et al. Elevated GDNF levels following viral vector-mediated gene transfer can increase neuronal death after stroke in rats. Neurobiol Dis 2003;14:542-556.
96. Georgievska B, Kirik D, and Bjorklund A. Aberrant sprouting and downregulation of tyrosine hydroxylase in lesioned nigrostriatal dopamine neurons induced by long-lasting overexpression of glial cell line derived neurotrophic factor in the striatum by lentiviral gene transfer. Exp Neurol 2002;177:461-474.
97. Chtarto A, Bender HU, Hanemann CO, et al. Tetracycline-inducible transgene expression mediated by a single AAV vector. Gene Ther 2003; 10:84-94.
98. Bockstael O, Chtarto A, Wakkinen J, et al. Differential transgene expression profiles in rat brain, using rAAV2/1 vectors with tetracycline-inducible and cytomegalovirus promoters. Human Gene Ther 2008;19:1293-1305.
99. Maddalena A, Tereshchenko J, Bahr M, et al. Adeno-associated virus-mediated, mifepristoneregulated transgene expression in the brain. Mol Ther Nucleic Acids 2013;2:e106.
100. Tereshchenko J, Maddalena A, Bahr M, et al. Pharmacologically controlled, discontinuous GDNF gene therapy restores motor function in a rat model of Parkinson's disease. Neurobiol Dis 2014;65:35-42.
101. Iwamoto M, Bjorklund T, Lundberg C, et al. A general chemical method to regulate protein stability in the mammalian central nervous system. Chem Biol 2010;17:981-988.
102. Tai K, Quintino L, Isaksson C, et al. Destabilizing domains mediate reversible transgene expression in the brain. PLoS One 2012;7:e46269.
103. Cristina N, Chatellard-Causse C, Manier M, et al. GDNF: existence of a second transcript in the brain. Brain Res Mol Brain Res 1995;32: 354-357.
104. Suter-Crazzolara C, and Unsicker K. GDNF is expressed in two forms in many tissues outside the CNS. Neuroreport 1994;5:2486-2488.
105. Lonka-Nevalaita L, Lume M, Leppanen S, et al. Characterization of the intracellular localization, processing, and secretion of two glial cell linederived neurotrophic factor splice isoforms. J Neurosci 2010;30:11403-11413.
106. Apostolou A, Shen Y, Liang Y, et al. Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death. Exp Cell Res 2008;314:2454-2467.
107. Tadimalla A, Belmont PJ, Thuerauf DJ, et al. Mesencephalic astrocyte-derived neurotrophic factor is an ischemia-inducible secreted endoplasmic reticulum stress response protein in the heart. Circ Res 2008;103:1249-1258.
108. 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.
109. 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.
110. Taylor H, Barua N, Bienemann A, et al. Clearance and toxicity of recombinant methionyl human glial cell line-derived neurotrophic factor (r-metHu GDNF) following acute convection-enhanced delivery into the striatum. PLoS One 2013;8: e56186.
111. Ibanez CF. Emerging themes in structural biology of neurotrophic factors. Trends Neurosci 1998;21: 438-444.