Can population genomics guide future therapeutic gene transfer strategies for Parkinson’s disease?


Medical and surgical therapies for patients with Parkinson’s disease (PD) are typically considered and initiated upon development of clinical signs, especially therapeutic gene transfer therapies. Early clinical trials delivering transgenes within the brains of PD patients have confirmed their safety and suggested mild to moderate efficacy. Confirmatory phase III trials have yet to be undertaken with any of the current treatment regimens. During the development of PD gene therapy, mapping of the human genome was finalized and provides major insights into the normal and pathogenic genetic variabilities of populations. Genome wide association studies (GWAS) have expanded the genetic defects and risk factors accompanying clinical PD. Advanced genomic investigations may allow asymptomatic individuals with a high risk of developing PD, and evident presymptomatic nigrostriatal deficiencies, to consider early treatment approaches. Herein we propose that certain genomically and clinically defined PD patients may provide unique opportunities for testing neuronotrophic gene therapy in a pathobiological environment that is antecedent to overt motoric dysfunction. Such an approach may finally allow testing of the disease-altering capabilities of therapeutic gene transfer in PD.

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Fiandaca, M. , Padilla, R. , Conteh, I. and Federoff, H. (2013) Can population genomics guide future therapeutic gene transfer strategies for Parkinson’s disease?. Open Journal of Genetics, 3, 19-29. doi: 10.4236/ojgen.2013.32A1003.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] [1] Lees, A.J., Hardy, J. and Revesz, T. (2006) Parkinson’s disease. Lancet, 373, 2055-2066. doi:10.1016/S0140-6736(09)60492-X
[2] de Lau, L.M. and Breteler, M.M. (2006) Epidemiology of Parkinson’s disease. Lancet Neurology, 5, 525-535. doi:10.1016/S1474-4422(06)70471-9
[3] Wirdefeldt, K., Adami, H.O., Cole, P., Trichopoulos, D. and Mandel, J. (2011) Epidemiology and etiology of Parkinson’s disease: A review of the evidence. European Journal of Epidemiology, 26, S1-S58. doi:10.1007/s10654-011-9581-6
[4] Dorsey, E.R., Constantinescu, R., Thompson, J.P., Biglan, K.M., Holloway, R.G., Kieburtz, K., Marshall, F.J., Ravina, B.M., Schifitto, G., Siderowf, A. and Tanner, C.M. (2007) Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology, 68, 384-386. doi:10.1212/01.wnl.0000247740.47667.03
[5] Chen, J.J. (2010) Parkinson’s disease: Health-related quality of life, economic cost, and implications of early treatment. The American Journal of Managed Care, 16, S87-S93.
[6] Winter, Y.M., Balzer-Geldsetzer, A., Spottke, J.P., Reese, E., Baum, J., Klotsche, J., Rieke, A., Simonow, K., Eggert, W.H., Oertel and Dodel, R. (2010) Longitudinal study of the socioeconomic burden of Parkinson’s disease in Germany. European Journal of Neurology: The Official Journal of the European Federation of Neurological Societies, 17, 1156-1163.
[7] Winter, Y., Balzer-Geldsetzer, M., von Campenhausen, S., Spottke, A., Eggert, K., Oertel, W.H. and Dodel, R. (2010) Trends in resource utilization for Parkinson’s disease in Germany. Journal of Neurological Science, 294, 18-22. doi:10.1016/j.jns.2010.04.011
[8] Winter, Y., von Campenhausen, S., Reese, J.P., BalzerGeldsetzer, M., Longo, K., Spiga, G., Boetzel, K., Eggert, K., Oertel, W.H., Dodel, R. and Barone, P. (2010) Costs of Parkinson’s disease and antiparkinsonian pharmacotherapy: An Italian cohort study. Neuro-Degenerative Diseases, 7, 365-372. doi:10.1159/000302644
[9] Vossius, C., Nilsen, O.B. and Larsen, J.P. (2010) Parkinson’s disease and hospital admissions: Frequencies, diagnoses and costs. Acta Neurologica Scandinavica, 121, 38-43. doi:10.1111/j.1600-0404.2009.01239.x
[10] Lokk, J., Borg, S., Svensson, J., Persson, U. and Ljunggren, G. (2012) Drug and treatment costs in Parkinson’s disease patients in Sweden. Acta Neurologica Scandinavica, 125, 142-147. doi:10.1111/j.1600-0404.2011.01517.x
[11] Olanow, C.W., Stern, M.B. and Sethi, K. (2009) The scientific and clinical basis for the treatment of Parkinson disease. Neurology, 72, S1-S136. doi:10.1212/WNL.0b013e3181a1d44c
[12] Maguire-Zeiss, K.A. and Federoff, H.J. (2003) Convergent pathobiologic model of Parkinson’s disease. Annals of the New York Academy of Sciences, 991, 152-166. doi:10.1111/j.1749-6632.2003.tb07473.x
[13] Miller, R.M. and Federoff, H.J. (2005) Altered gene expression profiles reveal similarities and differences between Parkinson disease and model systems. The Neuroscientist: A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 11, 539-549.
[14] Schapira, A.H., Agid, Y., Barone, P., Jenner, P., Lemke, M.R., Poewe, W., Rascol, O., Reichmann, H. and Tolosa, E. (2009) Perspectives on recent advances in the understanding and treatment of Parkinson’s disease. European Journal of Neurology: The Official Journal of the European Federation of Neurological Societies, 16, 1090-1099.
[15] Hornykiewicz, O. (1975) Brain monoamines and parkinsonism. National Institute on Drug Abuse Research Monograph Series, 3, 13-21.
[16] Forno, L.S. (1996) Neuropathology of Parkinson’s disease. Journal of Neuropathology & Experimental Neurology, 55, 259-272. doi:10.1097/00005072-199603000-00001
[17] Wichmann, T. and DeLong, M.R. (1998) Models of basal ganglia function and pathophysiology of movement disorders. Neurosurgery Clinics of North America, 9, 223-236.
[18] Hoehn, M.M. and Yahr, M.D. (1967) Parkinsonism: Onset, progression and mortality. Neurology, 17, 427-442. doi:10.1212/WNL.17.5.427
[19] Braak, H., Del Tredici, K., Rub, U., de Vos, R.A., Jansen Steur, E.N. and Braak, E. (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24, 197-211. doi:10.1016/S0197-4580(02)00065-9
[20] Noyce, A.J., Bestwick, J.P., Silveira-Moriyama, L., Hawkes, C.H., Giovannoni, G., Lees, A.J. and Schrag, A. (2012) Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Annals of Neurology, 72, 893-901. doi:10.1002/ana.23687
[21] Postuma, R.B., Gagnon, J.F. and Montplaisir, J. (2010) Clinical prediction of Parkinson’s disease: Planning for the age of neuroprotection. Journal of Neurology, Neurosurgery, and Psychiatry, 81, 1008-1013. doi:10.1136/jnnp.2009.174748
[22] Fiandaca, M.S., Forsayeth, J. and Bankiewicz, K. (2008) Current status of gene therapy trials for Parkinson’s disease. Experimental Neurology, 209, 51-57. doi:10.1016/j.expneurol.2007.08.009
[23] Parkinson, J. (1817) An essay on the shaking palsy. Sherwood, Neely, and Jones, Paternoster Row, London.
[24] Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K. and Seitelberger, F. (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Journal of Neurological Science, 20, 415-455. doi:10.1016/0022-510X(73)90175-5
[25] Lloyd, K.G., Davidson, L. and Hornykiewicz, O. (1975) The neurochemistry of Parkinson’s disease: Effect of Ldopa therapy. Journal of Pharmacological and Experimental Therapy, 195, 453-464.
[26] Fiandaca, M.S., Bankiewicz, K.S. and Federoff, H.J. (2012) Gene therapy for the treatment of Parkinson’s disease: The nature of the biologics expands the future indications. Pharmaceuticals, 5, 553-590. doi:10.3390/ph5060553
[27] Richardson, R.M., Kells, A.P., Rosenbluth, K.H., Salegio, E.A., Fiandaca, M.S., Larson, P.S., Starr, P.A., Martin, A.J., Lonser, R.R., Federoff, H.J., Forsayeth, J.R. and Bankiewicz, K.S. (2011) Interventional MRI-guided putaminal delivery of AAV2-GDNF for a planned clinical trial in Parkinson’s disease. Molecular Therapy, 19, 1048-1057. doi:10.1038/mt.2011.11
[28] Su, X., Kells, A.P., Huang, E.J., Lee, H.S., Hadaczek, P., Beyer, J., Bringas, J., Pivirotto, P., Penticuff, J., Eberling, J., Federoff, H.J., Forsayeth, J. and Bankiewicz, K.S. (2009) Safety evaluation of AAV2-GDNF gene transfer into the dopaminergic nigrostriatal pathway in aged and parkinsonian rhesus monkeys. Human Gene Therapy, 20, 1627-1640. doi:10.1089/hum.2009.103
[29] Kordower, J.H., Herzog, C.D., Dass, B., Bakay, R.A., Stansell, J., Gasmi, M. and Bartus, R.T. (2006) Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. Annals of Neurology, 60, 706-715. doi:10.1002/ana.21032
[30] Marks, W.J., Bartus, R.T., Siffert, J., Davis, C.S., Lozano, A., Boulis, N., Vitek, J., Stacy, M., Turner, D., Verhagen, L., Bakay, R., Watts, R., Guthrie, B., Jankovic, J., Simpson, R., Tagliati, M., Alterman, R., Stern, M., Baltuch, G., Starr, P.A., Larson, P.S., Ostrem, J.L., Nutt, J., Kieburtz, K., Kordower, J.H. and Olanow, C.W. (2010) Gene delivery of AAV2-neurturin for Parkinson’s disease: A double-blind, randomised, controlled trial. Lancet Neurology, 9, 1164-1172. doi:10.1016/S1474-4422(10)70254-4
[31] Benabid, A.L. (2003) Deep brain stimulation for Parkinson’s disease. Current Opinion in Neurobiology, 13, 696-706. doi:10.1016/j.conb.2003.11.001
[32] Schmutz, J., Wheeler, J., Grimwood, J., Dickson, M., Yang, J., Caoile, C., Bajorek, E., Black, S., Chan, Y.M., Denys, M., Escobar, J., Flowers, D., Fotopulos, D., Garcia, C., Gomez, M., Gonzales, E., Haydu, L., Lopez, F., Ramirez, L., Retterer, J., Rodriguez, A., Rogers, S., Salazar, A., Tsai, M. and Myers, R.M. (2004) Quality assessment of the human genome sequence. Nature, 429, 365-368. doi:10.1038/nature02390
[33] Jorde, L.B., Watkins, W.S. and Bamshad, M.J. (2001) Population genomics: A bridge from evolutionary history to genetic medicine. Human Molecular Genetics, 10, 2199-2207. doi:10.1093/hmg/10.20.2199
[34] Bush, W.S. and Moore, J.H. (2012) Chapter 11: Genomewide association studies. PLoS Computing Biology, 8, e1002822. doi:10.1371/journal.pcbi.1002822
[35] International HapMap (2003) The International HapMap Project. Nature, 426, 789-796. doi:10.1038/nature02168
[36] Moore, J.H., Asselbergs, F.W. and Williams, S.M. (2010) Bioinformatics challenges for genome-wide association studies. Bioinformatics, 26, 445-455. doi:10.1093/bioinformatics/btp713
[37] Mirelman, A., Gurevich, T., Giladi, N., Bar-Shira, A., Orr-Urtreger, A. and Hausdorff, J.M. (2011) Gait alterations in healthy carriers of the LRRK2 G2019S mutation. Annals of Neurology, 69, 193-197. doi:10.1002/ana.22165
[38] Hausdorff, J.M., Balash, J. and Giladi, N. (2003) Effects of cognitive challenge on gait variability in patients with Parkinson’s disease. Journal of Geriatric Psychiatry and Neurology, 16, 53-58.
[39] Maetzler, W. and Hausdorff, J.M. (2012) Motor signs in the prodromal phase of Parkinson’s disease. Movement Disorders, 27, 627-633.
[40] Kumar, K.R., Djarmati-Westenberger, A. and Grunewald, A. (2011) Genetics of Parkinson’s disease. Seminars in Neurology, 31, 433-440. doi:10.1055/s-0031-1299782
[41] Tan, E.K., Kwok, H.H., Tan, L.C., Zhao, W.T., Prakash, K.M., Au, W.L., Pavanni, R., Ng, Y.Y., Satake, W., Zhao, Y., Toda, T. and Liu, J.J. (2010) Analysis of GWASlinked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus. Neurology, 75, 508-512. doi:10.1212/WNL.0b013e3181eccfcd
[42] Hauser, M.A., Li, Y.J., Xu, H., Noureddine, M.A., Shao,Y.S., Gullans, S.R., Scherzer, C.R., Jensen, R.V., McLaurin, A.C., Gibson, J.R., Scott, B.L., Jewett, R.M., Stenger, J.E., Schmechel, D.E., Hulette, C.M. and Vance, J.M. (2005) Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with Parkinsonism. Archives of Neurology, 62, 917-921. doi:10.1001/archneur.62.6.917
[43] Moran, L.B., Duke, D.C., Deprez, M., Dexter, D.T., Pearce, R.K. and Graeber, M.B. (2006) Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson’s disease. Neurogenetics, 7, 1-11. doi:10.1007/s10048-005-0020-2
[44] Moran, L.B. and Graeber, M.B. (2008) Towards a pathway definition of Parkinson’s disease: A complex disorder with links to cancer, diabetes and inflammation. Neurogenetics, 9, 1-13. doi:10.1007/s10048-007-0116-y
[45] Scherzer, C.R., Jensen, R.V., Gullans, S.R. and Feany, M.B. (2003) Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson’s disease. Human Molecular Genetics, 12, 2457-2466. doi:10.1093/hmg/ddg265
[46] Miller, R.M. and Federoff, H.J. (2006) Microarrays in Parkinson’s disease: A systematic approach. NeuroRX, 3, 319-326. doi:10.1016/j.nurx.2006.05.008
[47] Simunovic, F., Yi, M., Wang, Y., Macey, L., Brown, L.T., Krichevsky, A.M., Andersen, S.L., Stephens, R.M., Benes, F.M. and Sonntag, K.C. (2009) Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson’s disease pathology. Brain, 132, 1795-1809.
[48] Grunblatt, E., Mandel, S., Jacob-Hirsch, J., Zeligson, S., Amariglo, N., Rechavi, G., Li, J., Ravid, R., Roggendorf, W., Riederer, P. and Youdim, M. B. (2004) Gene expression profiling of Parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. Journal of Neural Transmission, 111, 1543-1573. doi:10.1007/s00702-004-0212-1
[49] Sirbu, A., Kerr, G., Crane, M. and Ruskin, H.J. (2012) RNA-Seq vs dual- and single-channel microarray data: Sensitivity analysis for differential expression and clustering. PloS One, 7, e50986. doi:10.1371/journal.pone.0050986
[50] Scherzer, C.R., Offe, K., Gearing, M., Rees, H.D., Fang, G., Heilman, C.J., Schaller, C., Bujo, H., Levey, A.I. and Lah, J.J. (2004) Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Archives of Neurology, 61, 1200-1205. doi:10.1001/archneur.61.8.1200
[51] Scherzer, C.R. (2009) Chipping away at diagnostics for neurodegenerative diseases. Neurobiology of Disease, 35, 148-156. doi:10.1016/j.nbd.2009.02.016
[52] Schadt, E.E., Lamb, J., Yang, X., Zhu, J., Edwards, S., Guhathakurta, D., Sieberts, S.K., Monks, S., Reitman, M., Zhang, C., Lum, P.Y., Leonardson, A., Thieringer, R., Metzger, J.M., Yang, L., Castle, J., Zhu, H., Kash, S.F., Drake, T.A., Sachs, A. and Lusis, A.J. (2005) An integrative genomics approach to infer causal associations between gene expression and disease. Nature Genetics, 37, 710-717.
[53] Scherzer, C.R., Eklund, A.C., Morse, L.J., Liao, Z., Locascio, J.J., Fefer, D., Schwarzschild, M.A., Schlossmacher, M.G., Hauser, M.A., Vance, J.M., Sudarsky, L.R., Standaert, D.G., Growdon, J.H., Jensen R.V. and Gullans, S.R. (2007) Molecular markers of early Parkinson’s disease based on gene expression in blood. Proceedings of the National Academy of Sciences of the United States of America, 104, 955-960. doi:10.1073/pnas.0610204104
[54] Scherzer, C.R., Grass, J.A., Liao, Z., Pepivani, I., Zheng, B., Eklund, A.C., Ney, P.A., Ng, J., McGoldrick, M., Mollenhauer, B., Bresnick, E.H. and Schlossmacher, M.G. (2008) GATA transcription factors directly regulate the Parkinson's disease-linked gene alpha-synuclein. Proceedings of the National Academy of Sciences of the United States of America, 105, 10907-10912. doi:10.1073/pnas.0802437105
[55] Zheng, B., Liao, Z., Locascio, J.J., Lesniak, K.A., Roderick, S.S., Watt, M.L., Eklund, A.C., Zhang-James, Y., Kim, P.D., Hauser, M.A., Grunblatt, E., Moran, L. B., Mandel, S.A., Riederer, P., Miller, R.M., Federoff, H.J., Wullner, U., Papapetropoulos, S., Youdim, M.B., Cantuti-Castelvetri, I., Young, A.B., Vance, J.M., Davis, R.L., Hedreen, J.C., Adler, C.H., Beach, T.G., Graeber, M.B., Middleton, F.A., Rochet, J.C., Scherzer C.R. and Global, P.D.G.E.C. (2010) PGC-1alpha, a potential therapeutic target for early intervention in Parkinson’s disease. Science Translational Medicine, 2, 52ra73. doi:10.1126/scitranslmed.3001059
[56] Scholz, S.W., Mhyre, T., Ressom, H., Shah S. and Federoff, H.J. (2012) Genomics and bioinformatics of Parkinson’s disease. Cold Spring Harbor Perspectives in Medicine, 2, a009449.
[57] Peeraully T. and Tan, E.K. (2012) Genetic variants in sporadic Parkinson’s disease: East vs west. Parkinsonism & Related Disorders, 18, S63-S65. doi:10.1016/S1353-8020(11)70021-9
[58] Lang, A.E. (2011) A critical appraisal of the premotor symptoms of Parkinson’s disease: Potential usefulness in early diagnosis and design of neuroprotective trials. Movement Disorders, 26, 775-783.
[59] Van Nuenen, B.F., van Eimeren, T., van der Vegt, J.P., Buhmann, C., Klein, C., Bloem B.R. and Siebner, H.R. (2009) Mapping preclinical compensation in Parkinson’s disease: An imaging genomics approach. Movement Disorders, 24, S703-S710.
[60] Fiandaca, M.S. and Bankiewicz, K.S. (2010) Gene therapy for Parkinson’s disease: From nonhuman primates to humans. Current Opinion in Molecular Therapeutics, 12, 519-529.
[61] Muramatsu, S., Fujimoto, K., Kato, S., Mizukami, H., Asari, S., Ikeguchi, K., Kawakami, T., Urabe, M., Kume, A., Sato, T., Watanabe, E., Ozawa, K. and Nakano, I. (2010) A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease. Molecular Therapy, 18, 1731-1735.
[62] Christine, C.W., Starr, P.A., Larson, P.S., Eberling, J.L., Jagust, W.J., Hawkins, R.A., Van Brocklin, H.F., Wright, J.F., Bankiewicz, K.S. and Aminoff, M.J. (2009) Safety and tolerability of putaminal gene therapy for Parkinson’s disease. Neurology, 73, 1662-1669. doi:10.1212/WNL.0b013e3181c29356
[63] Zrinzo, L., Foltynie, T., Limousin, P. and Hariz, M.I. (2012) Reducing hemorrhagic complications in functional neurosurgery: A large case series and systematic literature review. Journal of Neurosurgery, 116, 84-94. doi:10.3171/2011.8.JNS101407
[64] Richardson, R.M., Kells, A.P., Martin, A.J., Larson, P.S., Starr, P.A., Piferi, P.G., Bates, G., Tansey, L., Rosenbluth, K.H., Bringas, J.R., Berger, M.S. and Bankiewicz, K.S. (2011) Novel platform for MRI-guided convection-enhanced delivery of therapeutics: Preclinical validation in nonhuman primate brain. Stereotactic and Functional Neurosurgery, 89, 141-151. doi:10.1159/000323544
[65] Wilson, J.M., Levey, A.I., Rajput, A., Ang, L., Guttman, M., Shannak, K., Niznik, H.B., Hornykiewicz, O., Pifl, C. and Kish, S.J. (1996) Differential changes in neurochemical markers of striatal dopamine nerve terminals in idiopathic Parkinson’s disease. Neurology, 47, 718-726. doi:10.1212/WNL.47.3.718
[66] Fearnley, J.M. and Lees, A.J. (1991) Ageing and Parkinson’s disease: Substantia nigra regional selectivity. Brain, 114, 2283-2301.
[67] Kaplitt, M.G., Feigin, A., Tang, C., Fitzsimons, H.L., Mattis, P., Lawlor, P.A., Bland, R.J., Young, D., Strybing, K., Eidelberg, D. and During, M.J. (2007) 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. The Lancet, 369, 2097-2105. doi:10.1016/S0140-6736(07)60982-9
[68] LeWitt, P.A., Rezai, A.R., Leehey, M.A., Ojemann, S.G., Flaherty, A.W., Eskandar, E.N., Kostyk, S.K., Thomas, K., Sarkar, A., Siddiqui, M.S., Tatter, S.B., Schwalb, J.M., Poston, K.L., Henderson, J.M., Kurlan, R.M., Richard, I.H., Van Meter, L., Sapan, C.V., During, M.J., Kaplitt, M.G. and Feigin, A. (2011) AAV2-GAD gene therapy for advanced Parkinson’s disease: A double-blind, shamsurgery controlled, randomised trial. The Lancet Neurology, 10, 309-319. doi:10.1016/S1474-4422(11)70039-4
[69] Annett, L.E., Dunnett, S.B., Martel, F.L., Rogers, D.C., Ridley, R.M., Baker, H.F. and Marsden, C.D. (1990) A functional assessment of embryonic dopaminergic grafts in the marmoset. Progress in Brain Research, 82, 535-542. doi:10.1016/S0079-6123(08)62644-8
[70] Eberling, J.L., Jagust, W.J., Christine, C.W., Starr, P., Larson, P., Bankiewicz, K.S. and Aminoff, M.J. (2008) Results from a phase I safety trial of hAADC gene therapy for Parkinson’s disease. Neurology, 70, 1980-1983. doi:10.1212/01.wnl.0000312381.29287.ff
[71] Valles, F., Fiandaca, M.S., Eberling, J.L., Starr, P.A., Larson, P.S., Christine, C.W., Forsayeth, J., Richardson, R.M., Su, X., Aminoff, M.J. and Bankiewicz, K.S. (2010) 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, 67, 1377-1385.
[72] Hwu, W.L., Muramatsu, S., Tseng, S.H., Tzen, K.Y., Lee, N.C., Chien, Y.H., Snyder, R.O., Byrne, B.J., Tai, C.H. and Wu, R.M. (2012) Gene therapy for aromatic L-amino acid decarboxylase deficiency. Science Transnational Medicine, 4, 134ra161.
[73] Marks, W.J., Ostrem, J.L., Verhagen, L., Starr, P.A., Larson, P.S., Bakay, R.A.E., Taylor, R., Cahn-Weiner, D.A., Stoessl, A.J., Olanow, C.W. and Bartus, R.T. (2008) 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 Neurology, 7, 400-408.
[74] Herzog, C.D., Dass, B., Holden, J.E., Stansell, J. 3rd, Gasmi, M., Tuszynski, M.H., Bartus, R.T. and Kordower, J.H. (2007) Striatal delivery of CERE-120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys. Movement Disorders, 22, 1124-1132.
[75] Ceregene (2009) A phase I/II trial assessing the safety and efficacy of bilateral intraputaminal and intranigral administration of CERE-120 (Adeno-associated virus serotype 2 [AAV2]-neurturin [NTN]) in subjects with idiopathic Parkinson’s disease (06/17/2009).
[76] Bartus, R.T., Herzog, C.D., Chu, Y., Wilson, A., Brown, L., Siffert, J., Johnson Jr., E.M., Olanow, C.W., Mufson E.J. and Kordower, J.H. (2011) Bioactivity of AAV2neurturin gene therapy (CERE-120): Differences between Parkinson’s disease and nonhuman primate brains. Movement Disorders, 26, 27-36.
[77] Ceregene (2013) Press release-ceregene reports data from Parkinson’s disease phase 2b study.
[78] Jarraya, B., Boulet, S., Ralph, G.S., Jan, C., Bonvento, G., Azzouz, M., Miskin, J.E., Shin, M., Delzescaux, T., Drouot, X., Herard, A.-S., Day, D.M., Brouillet, E., Kingsman, S.M., Hantraye, P., Mitrophanous, K.A., Mazarakis N.D. and Palfi, S. (2009) Dopamine gene therapy for Parkinson’s disease in a nonhuman primate without associated dyskinesia. Science Translational Medicine, 1, 1-10. doi:10.1126/scitranslmed.3000130
[79] Oxford Biomedica Press Release. (2011) Oxford biomedica announces interim update on prosavin® phase I/II study in Parkinson’s disease-15/12/2011.

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