Systematic Review Article

基因治疗对阿尔茨海默病认知功能恢复的疗效:系统综述

卷 21, 期 3, 2021

发表于: 20 January, 2021

页: [246 - 257] 页: 12

弟呕挨: 10.2174/1566523221666210120091146

价格: $65

摘要

背景:阿尔茨海默病(AD)是导致痴呆的主要原因,是一种进行性神经再生疾病,其特征是神经原纤维缠结和老年斑的积累。目前还没有治愈的方法;然而,一些治疗方法可以减缓疾病的进展,包括基因治疗,这被研究为治疗AD的巨大潜力。 目的:这篇综述的目的是确定基因治疗对恢复AD认知的有效性。 方法:系统综述采用了截至2020年5月发表在Web of Science、Scopus和Medline/PUBMED数据库上的论文。如果文章是研究基因治疗对AD认知的影响的原创研究,那么它们将被考虑纳入研究。使用动物干预研究的偏倚风险工具(SYRCLE的Rob工具)和Jadad量表对所选研究的方法质量进行评估。 结果:大多数临床前研究在改善小鼠的记忆和学习能力方面取得了积极的结果,这些小鼠接受了基因治疗。另一方面,临床研究尚未得出与用于基因治疗的病毒载体的传递方式有关的结论。 结论:基因治疗在临床前试验中显示了治疗AD的巨大潜力,但由于临床前研究在预测人类治疗效果方面存在局限性,因此对结果的解释应谨慎。

关键词: 痴呆症,治疗,认知,衰老,阿尔茨海默病,遗传

图形摘要
[1]
Association As. 2019 Alzheimer’s disease facts and figures. Alzheimers Dement 2019; 15(3): 321-87.
[http://dx.doi.org/10.1016/j.jalz.2019.01.010]
[2]
Van Cauwenberghe C, Van Broeckhoven C, Sleegers K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med 2016; 18(5): 421-30.
[http://dx.doi.org/10.1038/gim.2015.117] [PMID: 26312828]
[3]
Braak E, Griffing K, Arai K, Bohl J, Bratzke H, Braak H. Neuropathology of Alzheimer’s disease: what is new since A. Alzheimer? Eur Arch Psychiatry Clin Neurosci 1999; 249(3)(Suppl. 3): 14-22.
[http://dx.doi.org/10.1007/PL00014168] [PMID: 10654095]
[4]
Braak H, Braak E. Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol 1996; 92(2): 197-201.
[http://dx.doi.org/10.1007/s004010050508] [PMID: 8841666]
[5]
Terry RD, Masliah E, Salmon DP, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991; 30(4): 572-80.
[http://dx.doi.org/10.1002/ana.410300410] [PMID: 1789684]
[6]
Guo Q, Zheng X, Yang P, et al. Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer׳s disease. Acta Pharm Sin B 2019; 9(3): 590-603.
[http://dx.doi.org/10.1016/j.apsb.2018.12.010] [PMID: 31193846]
[7]
Wallach CJG, Lars G. Kang, James D. Gene Therapy Applications for Intervertebral Disc Degeneration. Gene Therapy and Disc Degeneration 2003; 28(15): 6.
[http://dx.doi.org/10.1097/01.BRS.0000076905.31596.DF]]
[8]
Gonçalves GAR, Paiva RMA. Gene therapy: advances, challenges and perspectives. Einstein (Sao Paulo) 2017; 15(3): 369-75.
[http://dx.doi.org/10.1590/s1679-45082017rb4024] [PMID: 29091160]
[9]
Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement. Ann Intern Med 2009; 151(4): 264-269, W64.
[http://dx.doi.org/10.7326/0003-4819-151-4-200908180-00135] [PMID: 19622511]
[10]
Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 2014; 14(1): 43.
[http://dx.doi.org/10.1186/1471-2288-14-43] [PMID: 24667063]
[11]
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17(1): 1-12.
[http://dx.doi.org/10.1016/0197-2456(95)00134-4] [PMID: 8721797]
[12]
Rafii MS, Tuszynski MH, Thomas RG, et al. AAV2-NGF Study Team. Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol 2018; 75(7): 834-41.
[http://dx.doi.org/10.1001/jamaneurol.2018.0233] [PMID: 29582053]
[13]
Castle MJ, Baltanás FC, Kovacs I, Nagahara AH, Barba D, Tuszynski MH. Postmortem Analysis in a Clinical Trial of AAV2-NGF Gene Therapy for Alzheimer’s Disease Identifies a Need for Improved Vector Delivery. Hum Gene Ther 2020; 31(7-8): 415-22.
[http://dx.doi.org/10.1089/hum.2019.367] [PMID: 32126838]
[14]
Gu H, Long D, Song C, Li X. Recombinant human NGF-loaded microspheres promote survival of basal forebrain cholinergic neurons and improve memory impairments of spatial learning in the rat model of Alzheimer’s disease with fimbria-fornix lesion. Neurosci Lett 2009; 453(3): 204-9.
[http://dx.doi.org/10.1016/j.neulet.2009.02.027] [PMID: 19429036]
[15]
Wang YJ, Gao CY, Yang M, et al. Intramuscular delivery of a single chain antibody gene prevents brain Aβ deposition and cognitive impairment in a mouse model of Alzheimer’s disease. Brain Behav Immun 2010; 24(8): 1281-93.
[http://dx.doi.org/10.1016/j.bbi.2010.05.010] [PMID: 20595065]
[16]
Iwasaki Y, Negishi T, Inoue M, Tashiro T, Tabira T, Kimura N. Sendai virus vector-mediated brain-derived neurotrophic factor expression ameliorates memory deficits and synaptic degeneration in a transgenic mouse model of Alzheimer’s disease. J Neurosci Res 2012; 90(5): 981-9.
[http://dx.doi.org/10.1002/jnr.22830] [PMID: 22252710]
[17]
Zhang YY Q, Lai T, Yang Y, Li G, Sun S. Effects of Small Interfering RNA Targeting Sphingosine Kinase-1 Gene on the Animal Model of Alzheimer’s Disease. Journal Huazhong University Science Technology 2013; 33(3): 6.
[http://dx.doi.org/10.1007/s11596-013-1136-5]
[18]
Wen X, Wang L, Liu Z, Liu Y, Hu J. Intracranial injection of PEG-PEI/ROCK II-siRNA improves cognitive impairment in a mouse model of Alzheimer’s disease. Int J Neurosci 2014; 124(9): 697-703.
[http://dx.doi.org/10.3109/00207454.2013.877014] [PMID: 24350994]
[19]
Chen P, Yan Q, Wang S, Wang C, Zhao P. Transfer of three transcription factors via a lentiviral vector ameliorates spatial learning and memory impairment in a mouse model of Alzheimer’s disease. Gene 2016; 587(1): 59-63.
[http://dx.doi.org/10.1016/j.gene.2016.04.032] [PMID: 27102892]
[20]
Wang QH, Wang YR, Zhang T, et al. Intramuscular delivery of p75NTR ectodomain by an AAV vector attenuates cognitive deficits and Alzheimer’s disease-like pathologies in APP/PS1 transgenic mice. J Neurochem 2016; 138(1): 163-73.
[http://dx.doi.org/10.1111/jnc.13616] [PMID: 26991827]
[21]
He Y, Pan S, Xu M, et al. Adeno-associated virus 9-mediated Cdk5 inhibitory peptide reverses pathologic changes and behavioral deficits in the Alzheimer’s disease mouse model. FASEB J 2017; 31(8): 3383-92.
[http://dx.doi.org/10.1096/fj.201700064R] [PMID: 28420695]
[22]
Li M, Yuan Y, Hu B, Wu L. Study on Lentivirus-Mediated ABCA7 Improves Neurocognitive Function and Related Mechanisms in the C57BL/6 Mouse Model of Alzheimer’s Disease. J Mol Neurosci 2017; 61(4): 489-97.
[http://dx.doi.org/10.1007/s12031-017-0889-x] [PMID: 28124230]
[23]
Zheng JY, Sun J, Ji CM, et al. Selective deletion of apolipoprotein E in astrocytes ameliorates the spatial learning and memory deficits in Alzheimer’s disease (APP/PS1) mice by inhibiting TGF-β/Smad2/STAT3 signaling. Neurobiol Aging 2017; 54: 112-32.
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.03.002] [PMID: 28366226]
[24]
Chavoshinezhad S, Mohseni Kouchesfahani H, Salehi MS, Pandamooz S, Ahmadiani A, Dargahi L. Intranasal interferon beta improves memory and modulates inflammatory responses in a mutant APP-overexpressing rat model of Alzheimer’s disease. Brain Res Bull 2019; 150: 297-306.
[http://dx.doi.org/10.1016/j.brainresbull.2019.06.015] [PMID: 31233762]
[25]
Park J, Lee SY, Shon J, et al. Adalimumab improves cognitive impairment, exerts neuroprotective effects and attenuates neuroinflammation in an Aβ1-40-injected mouse model of Alzheimer’s disease. Cytotherapy 2019; 21(6): 671-82.
[http://dx.doi.org/10.1016/j.jcyt.2019.04.054] [PMID: 31076196]
[26]
Zeng CY, Yang TT, Zhou HJ, et al. Lentiviral vector-mediated overexpression of Klotho in the brain improves Alzheimer’s disease-like pathology and cognitive deficits in mice. Neurobiol Aging 2019; 78: 18-28.
[http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.003] [PMID: 30851437]
[27]
Li Y, Wang Y, Wang J, et al. Expression of Neprilysin in Skeletal Muscle by Ultrasound-Mediated Gene Transfer (Sonoporation) Reduces Amyloid Burden for AD. Mol Ther Methods Clin Dev 2020; 17: 300-8.
[http://dx.doi.org/10.1016/j.omtm.2019.12.012] [PMID: 32021878]
[28]
Kanninen K, Heikkinen R, Malm T, et al. Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 2009; 106(38): 16505-10.
[http://dx.doi.org/10.1073/pnas.0908397106] [PMID: 19805328]
[29]
Pérez-González R, Alvira-Botero MX, Robayo O, et al. Leptin gene therapy attenuates neuronal damages evoked by amyloid-β and rescues memory deficits in APP/PS1 mice. Gene Ther 2014; 21(3): 298-308.
[http://dx.doi.org/10.1038/gt.2013.85] [PMID: 24430238]
[30]
Kemppainen S, Lindholm P, Galli E, et al. Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer’s disease as well as in wild-type mice. Behav Brain Res 2015; 291: 1-11.
[http://dx.doi.org/10.1016/j.bbr.2015.05.002] [PMID: 25975173]
[31]
Barros-Viegas AT, Carmona V, Ferreiro E, et al. miRNA-31 Improves Cognition and Abolishes Amyloid-β Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer’s Disease. Mol Ther Nucleic Acids 2020; 19: 1219-36.
[http://dx.doi.org/10.1016/j.omtn.2020.01.010] [PMID: 32069773]
[32]
Mukhamedyarov MA, Leushina AV, Tikhonova AE, et al. Intravenous Transplantation of Human Umbilical Cord Blood Mononuclear Cells Overexpressing Nerve Growth Factor Improves Spatial Memory in APP/PS1 Transgenic Mice with a Model of Alzheimer’s Disease. Bionanoscience 2017; 8(1): 473-80.
[http://dx.doi.org/10.1007/s12668-017-0497-9]
[33]
Petukhova EO, Mukhamedshina YO, Salafutdinov II, et al. Effects of Transplanted Umbilical Cord Blood Mononuclear Cells Overexpressing GDNF on Spatial Memory and Hippocampal Synaptic Proteins in a Mouse Model of Alzheimer’s Disease. J Alzheimers Dis 2019; 69(2): 443-53.
[http://dx.doi.org/10.3233/JAD-190150] [PMID: 30958382]
[34]
Tan VTY, Mockett BG, Ohline SM, et al. Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha prevents development of memory and plasticity deficits in a mouse model of Alzheimer’s disease. Mol Brain 2018; 11(1): 7.
[http://dx.doi.org/10.1186/s13041-018-0348-9] [PMID: 29426354]
[35]
Bustos FJ, Ampuero E, Jury N, et al. Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer’s disease mice. Brain 2017; 140(12): 3252-68.
[http://dx.doi.org/10.1093/brain/awx272] [PMID: 29155979]
[36]
Selles MC, Fortuna JTS, Zappa-Villar MF, et al. Adenovirus-Mediated Transduction of Insulin-Like Growth Factor 1 Protects Hippocampal Neurons from the Toxicity of Aβ Oligomers and Prevents Memory Loss in an Alzheimer Mouse Model. Mol Neurobiol 2020; 57(3): 1473-83.
[http://dx.doi.org/10.1007/s12035-019-01827-y] [PMID: 31760608]
[37]
Richard KL, Filali M, Préfontaine P, Rivest S. Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid beta 1-42 and delay the cognitive decline in a mouse model of Alzheimer’s disease. J Neurosci 2008; 28(22): 5784-93.
[http://dx.doi.org/10.1523/JNEUROSCI.1146-08.2008] [PMID: 18509040]
[38]
Ryan DA, Mastrangelo MA, Narrow WC, Sullivan MA, Federoff HJ, Bowers WJ. 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): 1471-81.
[http://dx.doi.org/10.1038/mt.2010.111] [PMID: 20551911]
[39]
Hafez DM, Huang JY, Richardson JC, Masliah E, Peterson DA, Marr RA. F-spondin gene transfer improves memory performance and reduces amyloid-β levels in mice. Neuroscience 2012; 223: 465-72.
[http://dx.doi.org/10.1016/j.neuroscience.2012.07.038] [PMID: 22863679]
[40]
Kiyota T, Ingraham KL, Swan RJ, Jacobsen MT, Andrews SJ, Ikezu T. AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice. Gene Ther 2012; 19(7): 724-33.
[http://dx.doi.org/10.1038/gt.2011.126] [PMID: 21918553]
[41]
Kiyota T, Zhang G, Morrison CM, et al. AAV2/1 CD74 Gene Transfer Reduces β-amyloidosis and Improves Learning and Memory in a Mouse Model of Alzheimer’s Disease. Mol Ther 2015; 23(11): 1712-21.
[http://dx.doi.org/10.1038/mt.2015.142] [PMID: 26227349]
[42]
Spilman PR, Corset V, Gorostiza O, et al. Netrin-1 Interrupts Amyloid-β Amplification, Increases sAβPPα in vitro and in vivo, and Improves Cognition in a Mouse Model of Alzheimer’s Disease. J Alzheimers Dis 2016; 52(1): 223-42.
[http://dx.doi.org/10.3233/JAD-151046] [PMID: 27060954]
[43]
Embury CM, Dyavarshetty B, Lu Y, et al. Cathepsin B Improves ß-Amyloidosis and Learning and Memory in Models of Alzheimer’s Disease. J Neuroimmune Pharmacol 2017; 12(2): 340-52.
[http://dx.doi.org/10.1007/s11481-016-9721-6] [PMID: 27966067]
[44]
Martinez-Losa M, Tracy TE, Ma K, et al. 1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer’s Disease. Neuron 2018; 98(1): 75-89.
[http://dx.doi.org/10.1016/j.neuron.2018.02.029]]
[45]
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3): 189-98.
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204]
[46]
Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958; 8(3): 271-6.
[http://dx.doi.org/10.2466/pms.1958.8.3.271]
[47]
Sunderland T, Hill JL, Mellow AM, et al. Clock drawing in Alzheimer’s disease. A novel measure of dementia severity. J Am Geriatr Soc 1989; 37(8): 725-9.
[http://dx.doi.org/10.1111/j.1532-5415.1989.tb02233.x] [PMID: 2754157]
[48]
Wechsler D. Wechsler adult intelligence scale–Fourth Edition (WAIS–IV).San Antonio, TX: NCS Pearson. 2008; 22: p. 498.
[http://dx.doi.org/10.1177/0081246316654805]
[49]
Zekanowski C, Religa D, Graff C, Filipek S, Kuźnicki J. Genetic aspects of Alzheimer’s disease. Acta Neurobiol Exp (Warsz) 2004; 64(1): 19-31.
[PMID: 15190677]
[50]
Zhang S, Wang P, Ren L, Hu C, Bi J. Protective effect of melatonin on soluble Aβ1-42-induced memory impairment, astrogliosis, and synaptic dysfunction via the Musashi1/Notch1/Hes1 signaling pathway in the rat hippocampus. Alzheimers Res Ther 2016; 8(1): 40.
[http://dx.doi.org/10.1186/s13195-016-0206-x] [PMID: 27630117]
[51]
Giuffrida ML, Caraci F, Pignataro B, et al. Beta-amyloid monomers are neuroprotective. J Neurosci 2009; 29(34): 10582-7.
[http://dx.doi.org/10.1523/JNEUROSCI.1736-09.2009] [PMID: 19710311]
[52]
Walton EL. For better or worse: Immune system involvement in Alzheimer’s Disease. Biomed J 2018; 41(1): 1-4.
[http://dx.doi.org/10.1016/j.bj.2018.03.001] [PMID: 29673548]
[53]
Roberson ED, Halabisky B, Yoo JW, et al. Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer’s disease. J Neurosci 2011; 31(2): 700-11.
[http://dx.doi.org/10.1523/JNEUROSCI.4152-10.2011] [PMID: 21228179]
[54]
Campbell DJ. Neprilysin Inhibitors and Bradykinin. Front Med (Lausanne) 2018; 5: 257.
[http://dx.doi.org/10.3389/fmed.2018.00257] [PMID: 30283782]
[55]
Kuro-o M. Klotho and the aging process. Korean J Intern Med (Korean Assoc Intern Med) 2011; 26(2): 113-22.
[http://dx.doi.org/10.3904/kjim.2011.26.2.113] [PMID: 21716585]

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