|
|
|
| Development of Gene Therapy for Parkinson’s Disease And Alzheimer’s Disease |
| FAN Fu1,2, CHEN Jian-guo1, REN Hong-wei1,2 |
1. School of Life Sciences, Peking University, Beijing 100871, China;
2. R&D Center of Xiamen Bioway Biotech. Co. LTD., Xiamen 361009, China |
|
|
|
Abstract Alzheimer’s and Parkinson’s diseases represent the most prevalent neurodegenerative disorders worldwide. Current pharmacological or surgical treatments provide symptomatic benefits, but none can delay or stop the progression of these diseases. In recent years, the development of molecular biology and medicine has benefited for the understanding of Alzheimer’ s and Parkinson’ s diseases and prompted the research of gene therapy for them.An overview of the current efforts in the field for the treatment of Alzheimer’s and Parkinson’s diseases is presented. Against the pathogenesis of Parkinson’s disease and Alzheimer’s disease, there are several effective gene therapy strategies. It is no doubt that, gene therapy, as a novel treatment, is of great significance for understanding the causes, as well as comprehensive treatment for Parkinson’s disease and Alzheimer’s disease.
|
|
Received: 30 August 2012
Published: 25 April 2013
|
|
|
|
|
[1] Dauer W, Przedborski S. Parkinson’s disease: mechanisms and model. Neuron, 2003, 39(6): 889-909.
[2] Rui J N, Luís P A. Gene therapy for Parkinson’s and Alzheimer’s diseases: from the bench to clinical trials. Current Pharmaceutical Design, 2011, 17(31): 3434-3445.
[3] Jankovic J. Complications and limitations of drug therapy for Parkinson’s disease. Neurology, 2000, 55(12 Suppl 6): S2-6.
[4] Azzouz M, Martin-Rendon E, Barber R D, et al. Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson’s disease. J Neurosci, 2002, 22(23): 10302-103012.
[5] Muramatsu S, Fujimoto K, Ikeguchi K, et al. Behavioral recovery in a primate model of Parkinson’s disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes. Hum Gene Ther, 2002, 13(3): 345-354.
[6] Shen Y, Muramatsu S I, Ikeguchi K, et al. Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic-L-amino-acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson’s disease. Hum Gene Ther, 2000, 11(11): 1509-1519.
[7] Oxford bioMedica announces top-line results from six month follow-up of third patient cohort in ProSavin? Phase I/II study in Parkinson’s disease. Oxford Biomedica press release, 2011, http://www.oxfordbiomedica.co.uk/page.asp?pageid= 59&newsid=287.
[8] Bankiewicz K S, Forsayeth J, Eberling J L, et al. Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol Ther, 2006, 14(4): 564-5670.
[9] Hadaczek P, Eberling J L, Pivirotto P, et al. Eight years of clinical improvement in MPTP-lesioned primates after gene therapy with AAV2-hAADC. Mol Ther, 2010, 18(8): 1458-1461.
[10] Muramatsu S, Fujimoto K, Kato S, et al. A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease. Mol Ther, 2010, 18(9): 1731-1735.
[11] Lin L F, Doherty D H, Lile J D, et al. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science, 1993, 260(5111): 1130-1132.
[12] Chen Y H, Harvey B K, Hoffman A F, et al. MPTP-induced deficits in striatal synaptic plasticity are prevented by glial cell line-derived neurotrophic factor expressed via an adeno-associated viral vector. FASEB J, 2008, 22:261-275.
[13] Eberling J L, Kells A P, 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.
[14] Johnston L C, Eberling J, Pivirotto P, et al. Clinically relevant effects of AAV2-GDNF on the dopaminergic nigrostriatal pathway in aged Rhesus monkeys. Hum Gene Ther, 2009, 20(5):497-510.
[15] Brizard M, Carcenac C, Bemelmans A P, et al. Functional reinnervation from remaining DA terminals induced by GDNF lentivirus in a rat model of early Parkinson’s disease. Neurobiol Dis, 2006, 21:90-101.
[16] Palfi S, Leventhal L, Chu Y, et al. Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration. J Neurosci, 2002, 22:4942-4954.
[17] Smith A D, Kozlowski D A, Bohn M C, et al. Effect of AdGDNF on dopaminergic neurotransmission in the striatum of 6-OHDA-treated rats. Exp Neurol, 2005, 193(2):420-426.
[18] Sun M, Kong L, Wang X, et al. Comparison of the capability of GDNF, BDNF, or both, to protect nigrostriatal neurons in a rat model of Parkinson’s disease. Brain Res, 2005, 1052:119-129.
[19] Huang R Q, Ke W L, Liu Y, et al. Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model. J Neurol Sci, 2009, 29(1-2):123-130.
[20] Rosenblad C, Georgievska B, Kirik D. Long-term striatal overexpression of GDNF selectively downregulates tyrosine hydroxylase in the intact nigrostriatal dopamine system. Eur J Neurosci, 2003, 17(2):260-270.
[21] Sajadi A, Bauer M, Thony B, et al. Long-term glial cell line-derived neurotrophic factor overexpression in the intact nigrostriatal system in rats leads to a decrease of dopamine and increase of tetrahydrobiopterin production. J Neurochem, 2005, 93(6):1482-1486.
[22] Gasmi M, Brandon E P, Herzog C D, 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(1):67-76.
[23] Gasmi M, Herzog C D, Brandon E P, 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(1):62-68.
[24] Herzog C D, Brown L, Gammon D, et al. Expression, bioactivity, and safety 1 year after adeno-associated viral vector type 2-mediated delivery of neurturin to the monkey nigrostriatal system support cere-120 for Parkinson’s disease. Neurosurgery, 2009, 64(4):603-612.
[25] Herzog C D, Dass B, Gasmi M, et al. Transgene expression, bioactivity, and safety of CERE-120 (AAV2-neurturin) following delivery to the monkey striatum. Mol Ther, 2008, 16(10):1737-1744.
[26] Luo J, Kaplitt M G, Fitzsimons H L, et al. Subthalamic GAD gene therapy in a Parkinson’s disease rat model. Science, 2002, 298(5592): 425-429.
[27] Emborg M E, Carbon M, Holden J E, et al. Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. J Cereb Blood Flow Metab, 2007, 27(3): 501-509.
[28] Kaplitt M G, 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(9579): 2097-2105.
[29] Singleton A B, Farrer M, Johnson J, et al. alpha-Synuclein locus triplication causes Parkinson’s disease. Science, 2003, 302(5646): 841.
[30] Nishioka K, Hayashi S, Farrer M J, et al. Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson’s disease. Ann Neurol, 2006, 59(2): 298-309.
[31] Bellucci A, Navarria L, Zaltieri M, et al. Alpha-synuclein synaptic pathology and its implications in the development of novel therapeutic approaches to cure Parkinson’s disease. Brain Research. 2012, 1432(1): 95-113.
[32] Fountaine T M, Wade-Martins R. RNA interference-mediated knockdown of alpha-synuclein protects human dopaminergic neuroblastoma cells from MPP(+) toxicity and reduces dopamine transport. J Neurosci Res, 2007, 85(2): 351-363.
[33] Han Y, Khodr C E, Sapru M K, et al. A microRNA embedded AAV alpha-synuclein gene silencing vector for dopaminergic neurons. Brain Res, 2011, 1386: 15-24.
[34] Khandelwal P J, Dumanis S B, Feng L R, et al. Parkinson-related parkin reduces alpha-Synuclein phosphorylation in a gene transfer model. Mol Neurodegener, 2010, 5: 47.
[35] Nascimento-Ferreira I, Santos-Ferreira T, Sousa-Ferreira L, et al. Overexpression of the autophagic beclin-1 protein clears mutant ataxin-3 and alleviates Machado-Joseph disease. Brain, 2011, 134(Pt 5): 1400-1415.
[36] Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci, 1991, 12(10): 383-388.
[37] Tanzi R E, Bertram L. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell, 2005, 120(4): 545-555.
[38] Selkoe D J. Clearing the brain’s amyloid cobwebs. Neuron, 2001, 32(2): 177-180.
[39] Levi-Montalcini R. The nerve growth factor 35 years later. Science, 1987, 237(4819): 1154-1162.
[40] Lapchak P A, Araujo D M, Carswell S, et al. Distribution of nerve growth factor in the rat brain following a single intraventricular injection: correlation with the topographical distribution of trkA messenger RNA-expressing cells. Neuroscience, 1993, 54(2):445-460.
[41] Kromer L F. Nerve growth factor treatment after brain injury prevents neuronal death. Science, 1987, 235(4785): 214-216.
[42] Tuszynski M H, Sang H, Yoshida K, et al. Recombinant human nerve growth factor infusions prevent cholinergic neuronal degeneration in the adult primate brain. Ann Neurol, 1991, 30(5): 625-636.
[43] Eriksdotter Jonhagen M, Nordberg A, Amberla K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement Geriatr Cogn Disord, 1998, 9(5): 246-257.
[44] Rosenberg M B, Friedmann T, Robertson R C, et al. Grafting genetically modified cells to the damaged brain: restorative effects of NGF expression. Science, 1988, 242(4885): 1575-1578.
[45] Tuszynski M H, Roberts J, Senut M C, et al. Gene therapy in the adult primate brain: intraparenchymal grafts of cells genetically modified to produce nerve growth factor prevent cholinergic neuronal degeneration. Gene Ther, 1996, 3(4): 305-314.
[46] Smith D E, Roberts J, Gage F H, et al. Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. Proc Natl Acad Sci USA, 1999, 96(19): 10893-10898.
[47] Conner J M, Darracq M A, Roberts J, et al. Nontropic actions of neurotrophins: subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation. Proc Natl Acad Sci USA, 2001, 98(4): 1941-1946.
[48] Tuszynski M H, Thal L, Pay M, et al. A phase I clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med, 2005, 11(5): 551-555.
[49] Advanced encapsulated cell biodelivery product for Alzheimer’s disease successfully implanted in six patients. NsGene press release, 2008; http://nsgene.dk/NsGene-5.aspx?M=News&PID=15&NewsID=40.
[50] Nicoll J A, Wilkinson D, Holmes C, et al. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med, 2003, 9(4): 448-452.
[51] Holmes C, Boche D, Wilkinson D, et al. Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet, 2008, 372(9634): 216-223.
[52] Liu M, Acres B, Balloul J M, et al. Gene-based vaccines and immunotherapeutics. Proc Natl Acad Sci USA, 2004, 101(Suppl 2): 14567-14571.
[53] Bowers W J, Mastrangelo M A, Stanley H A, et al. HSV amplicon-mediated Abeta vaccination in Tg2576 mice: differential antigen-specific immune responses. Neurobiol Aging, 2005, 26(4): 393-407.
[54] Levites Y, Jansen K, Smithson L A, 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(46): 11923-11928.
[55] Ryan D A, Mastrangelo M A, Narrow W C, 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(8): 1471-1481.
[56] Iwata N, Tsubuki S, Takaki Y, et al. Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat Med, 2000, 6(2): 143-150.
[57] Iwata N, Tsubuki S, Takaki Y, et al. Metabolic regulation of brain Abeta by neprilysin. Science, 2001, 292(5521): 1550-1552.
[58] Marr R A, Rockenstein E, Mukherjee A, et al. Neprilysin gene transfer reduces human amyloid pathology in transgenic mice. J Neurosci, 2003, 23(6): 1992-1996.
[59] Hong C S, Goins W F, Goss J R, et al. Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer’s disease-related amyloid-beta peptide in vivo. Gene Ther, 2006, 13(14): 1068-1079.
[60] Lebson L, Nash K, Kamath S, et al. Trafficking CD11b-positive blood cells deliver therapeutic genes to the brain of amyloid-depositing transgenic mice. J Neurosci, 2010, 30(29): 9651-9658.
[61] Selkoe D J, Schenk D. Alzheimer’s disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol, 2003, 43: 545-584.
[62] Holsinger R M, McLean C A, Beyreuther K, et al. Increased expression of the amyloid precursor beta-secretase in Alzheimer’s disease. Ann Neurol, 2002, 51(6): 783-786.
[63] Singer O, Marr R A, Rockenstein E, et al. Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat Neurosci, 2005, 8(10): 1343-1349.
[64] Gong C X, Iqbal K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr Med Chem, 2008, 15(23): 2321-2328.
[65] Mazanetz M P, Fischer P M. Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases. Nat Rev Drug Discov, 2007, 6(6): 464-479.
[66] Piedrahita D, Hernandez I, Lopez-Tobon A, et al. Silencing of CDK5 reduces neurofibrillary tangles in transgenic Alzheimer’s mice. J Neurosci, 2010, 30(42): 13966-13976.
[67] Wolozin B. Cholesterol and the biology of Alzheimer’s disease. Neuron, 2004, 41(1): 7-10.
[68] Puglielli L, Tanzi R E, Kovacs D M. Alzheimer’s disease: the cholesterol connection. Nat Neurosci, 2003, 6(4): 345-351.
[69] Lund E G, Guileyardo J M, Russell D W. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci USA, 1999, 96(13): 7238-7243.
[70] Hudry E, Van Dam D, Kulik W, et al. Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer’s disease. Mol Ther, 2010, 18(1): 44-53.
[71] Manfredsson F P, Bloom D C, Mandel R J. Regulated protein expression for in vivo gene therapy for neurological disorders: progress, strategies, and issues. Neurobiology of Disease, 2012, 48: 212-221. |
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
