Treatment of Parkinson's disease: What's on the Horizon?

CNS Drugs

Volumn 19, Issue 9, 2005, Pages 723-743

  Wu, Stacy S ^a   Frucht, Steven J ^b  

^a UNIVERSITY HOSPITAL BASEL   (Switzerland)

^b NewYork Presbyterian Hospital   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 2 (2 FURYL) 7 (2 PHENYLETHYL)PYRAZOLO[4,3 E][1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE; 6 NITRO 7 SULFAMOYLBENZO[F]QUINOXALINE 2,3 DIONE; 6 QUINOXALINECARBOXYLIC ACID PIPERIDIDE; ADENOSINE A2A RECEPTOR ANTAGONIST; AMANTADINE; AMPA RECEPTOR AGONIST; AMPA RECEPTOR ANTAGONIST; ANTIOXIDANT; ANTIPARKINSON AGENT; APOMORPHINE; CAFFEINE; CARBIDOPA PLUS LEVODOPA; CEP 1347; DECAHYDRO 6 [2 (1H TETRAZOL 5 YL)ETHYL] 3 ISOQUINOLINECARBOXYLIC ACID; DOPAMINE RECEPTOR BLOCKING AGENT; DOPAMINE RECEPTOR STIMULATING AGENT; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GLUTAMATE ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID RECEPTOR ANTAGONIST; GLUTAMATE DECARBOXYLASE; ISTRADEFYLLINE; LEVODOPA; MEMANTINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NS 2330; PRAMIPEXOLE; SELEGILINE; TALAMPANEL; TOCOPHEROL; UBIDECARENONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRUS VECTOR;

ALZHEIMER DISEASE; BASAL GANGLION; BRAIN FUNCTION; CLINICAL TRIAL; DEGENERATIVE DISEASE; DEPRESSION; DETERIORATION; DIARRHEA; DISEASE COURSE; DISEASE EXACERBATION; DISEASE SEVERITY; DIZZINESS; DOPAMINERGIC NERVE CELL; DRUG ANTAGONISM; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; DYSKINESIA; GENE DELIVERY SYSTEM; GENE THERAPY; HEADACHE; HUMAN; LOW DRUG DOSE; MONOTHERAPY; MOTOR PERFORMANCE; NAUSEA; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PALLIATIVE THERAPY; PARKINSON DISEASE; PATHOGENESIS; PHYSICAL DISEASE BY BODY FUNCTION; PRIORITY JOURNAL; RECURRENT DISEASE; REVIEW; RIGIDITY; SIDE EFFECT; SUBTHALAMIC NUCLEUS; SYNCOPE;

ANIMALS; ANTIPARKINSON AGENTS; GENE THERAPY; HUMANS; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE;

EID: 24944582908     PISSN: 11727047     EISSN: None     Source Type: Journal    
DOI: 10.2165/00023210-200519090-00001     Document Type: Review

References (130)

1. Mouradian M. Recent advances in the genetics and pathogenesis of Parkinson's disease. Neurology 2002; 58 (2): 179-85
2. McNaught K, Mytilineou C, Jnobaptiste R, et al. Impairment of the ubiquitin-proteasome system causes dopaminergic cell death and inclusion body formation in the ventral mesence-phalic cultures. J Neurochem 2002; 81: 301-6
3. Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson's disease patients. Ann Neurol 1997; 42 (5): 747-55
4. Rinne UK, Larsen JP, Siden A, et al. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology 1998; 51: 1309-14
5. Ruottinen HM, Rinne UK. A double-blind pharmacokinetic and clinical dose-response study of entacapone as an adjuvant to levodopa therapy in advanced Parkinson's disease. Clin Neuropharmacol 1996; 19: 283-96
6. 2A antagonists as novel nondopaminergic therapy for motor dysfunction in PD. Neurology 2003; 61 Suppl. 6: S33-8
7. 2A antagonists. Neurology 2003; 61 Suppl. 6: S44-8
8. Penney Jr J, Young A. Striatal in homogeneities and basal ganglia origin. Mov Disord 1986; 1: 3-15
9. 2A receptor antagonist treatment of Parkinson's disease. Neurology 2003; 61: 293-6
10. Chase T, Oh J. Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications. Ann Neurol 2000; 27 Suppl. 1: S122-9
11. 2A receptors regulate the gene expression of striatopallidal and striatonigral neurons. J Neurosci 1993; 13: 1080-7
12. 2 dopamine receptors in rat striatum. Mol Brain Res 1992; 14: 186-95
13. Franco R, Ferre S, Agnati L, et al. Evidence for adenosine/dopamine receptor interactions: indications for heteromerization. Neuropsychopharmacology 2000; 23: S50-9
14. Feigin A. Nondopaminergic symptomatic therapies for Parkinson's disease. Neurology 2003; 61: 286-7
15. 2A and dopamine receptor interactions in basal ganglia of dopamine denervated rats. Neurology 2003; 61 Suppl. 6: S39-42
16. 2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 1998; 43: 507-13
17. 2A receptor antagonist istradefylline in advanced PD. Neurology 2003; 61: 297-303
18. Ruottinen HM, Rinne UK. COMT inhibition in the treatment of Parkinson's disease. J Neurol 1998; 245 Suppl. 3: 25-34
19. 2A antagonist KW-6002 with L-dopa or with selec-tive D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys. Exp Neurol 2000; 162: 321-7
20. 2A receptor antagonist in MPTP-treated monkeys. Neurology 1999; 52: 1673-7
21. Frucht S, Greene P, Fahn S. Sleep episodes in Parkinson's disease: a wake-up call. Mov Disord 2000; 15: 601-3
22. Frucht S, Rogers J, Greene P, et al. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology 1999; 52: 1908-10
23. Paus S, Brecht H, Köster J, et al. Sleep attacks, daytime sleepi-ness, and dopamine agonists in Parkinson's disease. Mov Disord 2003; 18: 659-67
24. Shaunak S, Wilkins A, Pillig J, et al. Pericardial, retroperitoneal, and pleural fibrosis induced by pergolide. J Neurol Neurosurg Psychiatry 1999; 66: 79-81
25. 2A receptor antagonists in animal models of Parkinson's disease. Neurology 2003; 61 Suppl. 6: S55-61
26. 2A receptors in neuroprotection of dopaminergic neurons. Neurology 2003; 61 Suppl. 6: S49-50
27. Hernàn M, Takkouche B, Caamaño-Isorna F, et al. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Ann Neurol 2002; 52: 276-84
28. Fall P, Fredrikson M, Axelson O, et al. Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-controlled study in southeastern Sweden. Mov Disord 1999; 14: 28-37
29. Ascherio A, Chen H. Caffeinated clues from epidemiology of Parkinson's disease. Neurology 2001; 61 Suppl. 6: S51-4
30. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. The Parkinson Study Group. N Engl J Med 1993; 328 (3): 176-83
31. Ward C. Does selegiline delay progression of Parkinson's disease? A critical re-evaluation of the DATATOP study. J Neurol Neurosurg Psychiatry 1994; 57: 217-20
32. Fahn S. Controversies in the therapy of Parkinson's disease. Adv Neurol 1996; 69: 477-86
33. Chase TN, Oh JD, Blanchet PJ. Neostriatal mechanisms in Parkinson's disease. Neurology 1998; 51 (2 Suppl. 2): S30-5
34. Chase TN, Engber TM, Mouradian MM. Contribution of dopaminergic and glutamatergic mechanisms to the pathogenesis of motor response complications in Parkinson's disease. Adv Neurol 1996; 69: 497-501
35. Calon F, Rajput AH, Hornykiewicz O, et al. Levodopa-induced motor complications are associated with alterations of glutamate receptors in Parkinson's disease. Neurobiol Dis 2003; 14 (3): 404-16
36. Hadj Tahar A, Gregoire L, Darre A, et al. Effect of a selective glutamate antagonist on L-dopa-induced dyskinesias in drug-naive parkinsonian monkeys. Neurobiol Dis 2004; 15 (2): 171-6
37. Merims D, Ziv I, Sherki Y, et al. The role of glutamatergic transmission in the pathogenesis of levodopa-induced dyskinesias: potential therapeutic approaches. Neurol Neurochir Pol 2001; 35 Suppl. 3: 65-8
38. Baas H. Dyskinesia in Parkinson's disease: pathophysiology and clinical risk factors. J Neurol 2000; 247 Suppl. 4: IV/12-6
39. Oh JD, Russell DS, Vaughan CL, et al. Enhanced tyrosine phosphorylation of striatal NMDA receptor subunits: effect of dopaminergic denervation and L-DOPA administration. Brain Res 1998; 813 (1): 150-9
40. Oh JD, Vaughan CL, Chase TN. Effect of dopamine denervation and dopamine agonist administration on serine phosphorylation of striatal NMDA receptor subunits. Brain Res 1999; 821 (2): 433-42
41. Chase TN. Levodopa therapy: consequences of the nonphysiologic replacement of dopamine. Neurology 1998; 50 (5 Suppl. 5): S17-25
42. Blanchet PJ, Konitsiotis S, Chase TN. Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys. Mov Disord 1998; 13 (5): 798-802
43. Papa SM, Chase TN. Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. Ann Neurol 1996; 39 (5): 574-8
44. Verhagen Metman L, Del Dotto P, van den Munckhof P, et al. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease. Neurology 1998; 50 (5): 1323-6
45. Danysz W, Parsons CG, Kornhuber J, et al. Aminoadamantanes as NMDA receptor antagonists and antiparkinsonian agents: preclinical studies. Neurosci Biobehav Rev 1997; 21 (4): 455-68
46. Konitsiotis S, Blanchet PJ, Verhagen L, et al. AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology 2000; 54 (8): 1589-95
47. Löschmann PA, Wullner U, Heneka MT, et al. Differential interaction of competitive NMDA and AMPA antagonists with selective dopamine D-1 and D-2 agonists in a rat model of Parkinson's disease. Synapse 1997; 26 (4): 381-91
48. Gossel M, Schmidt WJ, Loscher W, et al. Effect of coadministration of glutamate receptor antagonists and dopaminergic agonists on locomotion in monoamine-depleted rats. J Neural Transm Park Dis Dement Sect 1995; 10 (1): 27-39
49. Löschmann PA, Lange KW, Kunow M, et al. Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-dopa in models of Parkinson's disease. J Neural Transm Park Dis Dement Sect 1991; 3 (3): 203-13
50. Wachtel H, Kunow M, Loschmann PA. NBQX (6-nitrosulfamoyl-benzo- quinoxaline-dione) and CPP (3-carboxy-piperazin-propyl phosphonic acid) potentiate dopamine agonist induced rotations in substantia nigra lesioned rats. Neurosci Lett 1992; 142 (2): 179-82
51. Marin C, Jimenez A, Bonastre M, et al. Non-NMDA receptor-mediated mechanisms are involved in levodopa-induced motor response alterations in Parkinsonian rats. Synapse 2000; 36 (4): 267-74
52. Marin C, Jimenez A, Bonastre M, et al. LY293558, an AMPA glutamate receptor antagonist, prevents and reverses levodopa-induced motor alterations in Parkinsonian rats. Synapse 2001; 42 (1): 40-7
53. Young AB, Fagg GE. Excitatory amino acid receptors in the brain: membrane binding and receptor autoradiographic approaches. Trends Pharmacol Sci 1990; 11 (3): 126-33
54. Albin RL, Makowiec RL, Hollingsworth ZR, et al. Excitatory amino acid binding sites in the basal ganglia of the rat: a quantitative autoradiographic study. Neuroscience 1992; 46 (1): 35-48
55. Bernard V, Somogyi P, Bolam JP. Cellular, subcellular, and subsynaptic distribution of AMPA-type glutamate receptor subunits in the neostriatum of the rat. J Neurosci 1997; 17 (2): 819-33
56. Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 1998; 54 (5): 581-618
57. Carvalho AL, Kameyama K, Huganir RL. Characterization of phosphorylation sites on the glutamate receptor 4 subunit of the AMPA receptors. J Neurosci 1999; 19 (12): 4748-54
58. Derkach V, Barria A, Soderling TR. Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydrox-y-5-methyl-4-isoxazolepropionate type glutamate receptors. Proc Natl Acad Sci U S A 1999; 96 (6): 3269-74
59. Sheardown MJ, Nielsen EO, Hansen AJ, et al. 2,3-Dihydrox-y-6-nitro-7- sulfamoyl-benzo (F)quinoxaline: a neuroprotectant for cerebral ischemia. Science 1990; 247 (4942): 571-4
60. Johnson SA, Luu NT, Herbst TA, et al. Synergistic interactions between ampakines and antipsychotic drugs. J Pharmacol Exp Ther 1999; 289 (1): 392-7
61. Lodge D, Bond A, O'Neill MJ, et al. Stereoselective effects-of 2,3-benzodiazepines in vivo: electrophysiology and neuroprotection studies. Neuropharmacology 1996; 35 (12): 1681-8
62. Bleakman D, Ballyk BA, Schoepp DD, et al. Activity of 2,3-benzodiazepines at native rat and recombinant human glutamate receptors in vitro: stereospecificity and selectivity profiles. Neuropharmacology 1996; 35 (12): 1689-702
63. Bara-Jiminez W, Dimitrova T, Sherzai A, et al. Effect of monoamine reuptake inhibitor NS 2330 in advanced Parkinson's Disease. Mv Disord 2004; 19 (10): 1183-6
64. Wesnes K, Preskorn S, Friesen S, et al. NS2330 enhances cognitive function in normal volunteers and volunteers with possible Alzheimer's disease. Clin Pharmacol Ther 2002; 71 (2): 7
65. Thatte U. NS-2330 (Neurosearch). Curr Opin Investig Drugs 2001; 2 (11): 1592-4
66. A fourteen-week placebo-controlled dose-response efficacy and safety study of NS 2330 in early Parkinson's disease patients (study for proof of concept in early Parkinson's dis-ease of a triple reuptake inhibitor, NS 2330 / SCEPTRE) [online]. Available from URL: http://health.uchc.edu/clinical-trials/ trials.asp? Therap = Neurology&SubTherap = Parkin-son@s+Disease. [Accessed 2004 Aug 14]
67. Tran M, Mitchell T, Kennedy D, et al. Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy 2001; 7: 797-806
68. Huntington Study Group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurology 2001; 57 (3): 397-404
69. Przedborski S, Jackson-Lewis V. Mechanisms of MPTP toxicity. Mov Disord 1998; 13 Suppl. 1: 35-8
70. Krige D, Carroll M, Cooper J, et al. Platelet mitochondrial dysfunction in Parkinson's disease. Ann Neurol 1992; 32: 782-8
71. Parker Jr W, Boyson S, Parks J. Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Ann Neurol 1989; 26: 719-23
72. Turner C, Schapira A. Mitochondrial dysfunction in neurodegenerative disorders and ageing. Adv Exp Med Biol 2001; 487: 229-51
73. 10 supple-mentation provides mild symptomatic benefit in patients with Parkinson's disease. Neurosci Lett 2003; 341: 201-4
74. 10 attenuates the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice. Brain Res 1998; 783: 109-14
75. Matthews R, Yang L, Browne S, et al. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A 1998; 95: 8892-7
76. 10 in parkinsonian patients. Neurology 1998; 50: 793-5
77. 10 in early Parkinson disease. Arch Neurol 2002; 59: 1541-50
78. Hirsch EC, Hunot S, Faucheux B, et al. Dopaminergic neurons degenerate by apoptosis in Parkinson's disease. Mov Disord 1999; 14 (2): 383-5
79. Hartmann A, Hunot S, Michel PP, et al. Caspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. Proc Natl Acad Sci U S A 2000; 97 (6): 2875-80
80. Maroney AC, Finn JP, Bozyczko-Coyne D, et al. CEP-1347 (KT7515), an inhibitor of JNK activation, rescues sympathetic neurons and neuronally differentiated PC12 cells from death evoked by three distinct insults. J Neurochem 1999; 73 (5): 1901-12
81. Fanger GR, Gerwins P, Widmann C, et al. MEKKs, GCKs, MLKs, PAKs, TAKs, and tpls: upstream regulators of the c-Jun amino-terminal kinases? Curr Opin Genet Dev 1997; 7 (1): 67-74
82. Gallo KA, Johnson GL. Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat Rev Mol Cell Biol 2002; 3 (9): 663-72
83. Maroney AC, Finn JP, Connors TJ, et al. Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem 2001; 276 (27): 25302-8
84. Murakata C, Kaneko M, Gessner G, et al. Mixed lineage kinase activity of indolocarbazole analogues. Bioorg Med Chem Lett 2002; 12 (2): 147-50
85. Saporito MS, Brown EM, Miller MS, et al. CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons in vivo. J Pharmacol Exp Ther 1999; 288 (2): 421-7
86. Saporito MS, Thomas BA, Scott RW. MPTP activates c-Jun NH (2)-terminal kinase (JNK) and its upstream regulatory kinase MKK4 in nigrostriatal neurons in vivo. J Neurochem 2000; 75 (3): 1200-8
87. Parkinson Study Group. The safety and tolerability of a mixed lineage kinase inhibitor (CEP-1347) in PD. Neurology 2004; 62 (2): 330-2
88. PRECEPT: Parkinson Research Examination of CEP-1347 Trial [online]. Available from URL: http://www.parkinson-study-group.org. [Accessed 2004 Aug 14]
89. PRECEPT [online]. Available from URL: http://bidmc.harvard.edu/display. asp?.node_id = 1214. [Accessed 2004 Aug 14]
90. Lyons KE, Koller WC, Wilkinson SB, et al. Long term safety and efficacy of unilateral deep brain stimulation of the thalamus for parkinsonian tremor. J Neurol Neurosurg Psychiatry 2001; 71 (5): 682-4
91. Herzog J, Volkmann J, Krack P, et al. Two-year follow-up of subthalamic deep brain stimulation in Parkinson's disease. Mov Disord 2003; 18 (11): 1332-7
92. Luo J, Kaplitt M, Fitzsimons H, et al. Subthalamic GAD gene therapy in a Parkinson's disease rat model. Science 2002; 298 (5592): 425-9
93. During M, Kaplitt M, Stern M, et al. Subthalamic GAD gene transfer in Parkinson disease patients who are candidates for deep brain stimulation. Hum Gene Ther 2001; 12 (12): 1589-91
94. Grady D, Kolata G. Gene therapy used to treat patients with Parkinson's. New York Times 2003 Aug 19
95. Kordower J. In vivo gene delivery of glial cell line-derived neurotrophic factor for Parkinson's disease. Ann Neurol 2003; 53 Suppl. 3: S120-34
96. Björklund 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
97. 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: 767-73
98. Business wire. Update of neurologix phase I clinical trial of gene therapy for Parkinson's disease. Presented at AANS annual meeting; 2005 Apr 16-21; New Orleans (LA)
99. Federoff H. GAD Zooks! Excitement to inhibition in one easy step? Gene Ther 2003; 10: 365-6
100. Zurn A, Widmer H, Aebischer P. Sustained delivery of GDNF: towards a treatment for Parkinson's disease. Brain Res Rev 2001; 36: 222-9
101. Lapchak P, Gash D, Jiao S, et al. Glial cell line-derived neurotrophic factor: a novel therapeutic approach to treat motor dysfunction in Parkinson's disease. Exp Neurol 1997; 144: 29-34
102. Grondin R, Gash D. Glial cell line-derived neurotrophic factor (GDNF): a drug candidate for the treatment of Parkinson's disease. J Neurol 1998; 245 Suppl. 3: P35-42
103. Hou J, Lin L, Mytilinenou 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
104. Hudson J, Granholm A-C, Gerhardt G, et al. Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo. Brain Res Bull 1995; 36: 425-32
105. Kearns C, Gash DM. GDNF protects nigral dopamine neurons against 6-hydroxydopamine in vivo. Brain Res 1995; 672: 104-11
106. Kearns C, Cass WA, Smoot K, et al. GDNF protection against 6-OHDA: time dependence and requirement for protein syn-thesis. J Neurosci 1997; 17: 7111-8
107. Tomac A, Lindqvist E, Lin L-FH, et al. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 1995; 373: 335-9
108. 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: 107-11
109. Lapchak P, Miller P, Collins F, et al. Glial cell line-derived neurotrophic factor attenuates behavioural deficits and regulates nigrostriatal dopaminergic and peptidergic markers in 6-hydroxydopamine-lesioned adult rats: comparison of intraventricular and intranigral delivery. Neuroscience 1997; 78 (1): 61-72
110. Gash D, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996; 380: 252-5
111. Zhang Z, Miyoshi Y, Lapchak P, et al. Dose response to intraventricular glial cell line-derived neurotrophic factor administration in parkinsonian monkeys. J Pharmacol Exp Ther 1997; 282: 1396-401
112. 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: 208-14
113. Grondin R, Zhang Z, Yi A, et al. Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys. Brain 2002; 125: 2191-201
114. Nutt J, Burchiel K, Comella C, et al. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Neurology 2003; 60: 69-73
115. Kordower J, Palfi S, Chen E, et al. Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease. Ann Neurol 1999; 47 (3): 419-24
116. Gill S, Patel N, Hotton G, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson's disease. Nat Med 2003; 9 (5): 589-95
117. Wood MJ, Charlton HM, Wood KJ, et al. Immune responses to adenovius vectors in the nervous system. Trends Neurosci 1996; 19: 497-501
118. Kajiwara K, Byrnes AP, Charlton HM, et al. Immune responses to adenoviral vectors during gene transfer in the brain. Hum Gene Ther 1997; 8: 253-65
119. Rosenbald C, Gronborg M, Hansen C, et al. In vivo protection of nigral dopmaine neurons by lentiviral gene transfer of the novel GDNF-family member Neublastin/Artemin. Mol Cell Neurosci 2000; 15: 199-214
120. Mandel RJ, Snyder RO, Leff SE. Recombinant adeno-associated viral vector-mediated glial cell line-derived neurotrophic factor gene transfer protects nigral dopamine neurons after onset of progressive degeneration in a rat model of Parkinson's disease. Exp Neurol 1999; 160: 205-14
121. 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 Sci U S A 1997; 94: 14083-8
122. Kirik D, Rosenbald C, Björklund 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: 4686-700
123. Emborg M, Ma S, Mufson E, et al. Age-related declines in nigral neuronal function correlate with motor impairments in Rhesus monkeys. J Comp Neurol 1998; 401: 253-63
124. Bowenkamp K, David D, Lapchak P, et al. 6-hydroxydopamine induces the loss of the dopaminergic phenotype in substantia nigra neurons of the rat: a possible mechanism for restoration of the nigrostriatal circuit mediated by glial cell line-derived neurotrophic factor. Exp Brain Res 1996; 111: 1-7
125. Georgievska B, Kirik D, Björklund 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: 461-74
126. Lysaght MJ, Aebischer P. Encapsulated cells as therapy. Sci Am 1999; 280: 76-82
127. Lindner MD, Winn SR, Baetge EE, et al. Implantation of encapsulated catecholamine and GDNF-producing cells in rats with unilateral dopamine depletions and parkinsonian symptoms. Exp Neurol 1995; 132: 62-76
128. 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; 1: 325-33
129. Akerud P, Canals JM, Snyder EY, et al. Neuroprotection through delivery of glial cell-lined derived neurotrophic factor by neural stem cells in a mouse model of Parkinson's disease. J Neurosci 2001; 21: 8108-18
130. Freed C, Greene P, Breeze R, et al. Transplantation of embryon-ic dopamine neurons for severe Parkinson's disease. N Eng J Med 2001; 344 (10): 710-9