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Current Gene Therapy

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ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

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Challenges of Gene Therapy for Neurodegenerative Disorders

Author(s): Md. Sahab Uddin*, Zeeshan Ahmad Khan, Dewan Md. Sumsuzzman, Asma Perveen and Ghulam Md. Ashraf*

Volume 21, Issue 1, 2021

Published on: 05 November, 2020

Page: [3 - 10] Pages: 8

DOI: 10.2174/1566523220999201105150442

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Graphical Abstract

[1]
Borel F, Kay MA, Mueller C. Recombinant AAV as a platform for translating the therapeutic potential of RNA interference. Mol Ther 2014; 22(4): 692-701.
[http://dx.doi.org/10.1038/mt.2013.285] [PMID: 24352214]
[2]
Uddin MS, Al Mamun A, Asaduzzaman M, et al. Spectrum of disease and prescription pattern for outpatients with neurological disorders: an empirical pilot study in Bangladesh. Ann Neurosci 2018; 25(1): 25-37.
[http://dx.doi.org/10.1159/000481812] [PMID: 29887680]
[3]
Kabir MT, Sufian MA, Uddin MS, et al. NMDA receptor antagonists: repositioning of memantine as a multitargeting agent for alzheimer’s therapy. Curr Pharm Des 2019; 25(33): 3506-18.
[http://dx.doi.org/10.2174/1381612825666191011102444] [PMID: 31604413]
[4]
Kabir MT, Uddin MS, Begum MM, et al. Cholinesterase inhibitors for alzheimer’s disease: multitargeting strategy based on anti-alzheimer’s drugs repositioning. Curr Pharm Des 2019; 25(33): 3519-35.
[http://dx.doi.org/10.2174/1381612825666191008103141] [PMID: 31593530]
[5]
Ashraf GM, Uddin MS. Gene therapy for neuroprotection and neurorestoration (Part I). Curr Gene Ther 2020; 19(6): 358-8.
[http://dx.doi.org/10.2174/156652321906200324121208] [PMID: 32375609]
[6]
Ingusci S, Verlengia G, Soukupova M, Zucchini S, Simonato M. Gene therapy tools for brain diseases. Front Pharmacol 2019; 10: 724.
[http://dx.doi.org/10.3389/fphar.2019.00724] [PMID: 31312139]
[7]
Schlachetzki F, Zhang Y, Boado RJ, Pardridge WM. Gene therapy of the brain: the trans-vascular approach. Neurology 2004; 62(8): 1275-81.
[http://dx.doi.org/10.1212/01.WNL.0000120551.38463.D9] [PMID: 15111662]
[8]
Maguire CA, Ramirez SH, Merkel SF, Sena-Esteves M, Breakefield XO. Gene therapy for the nervous system: challenges and new strategies. Neurotherapeutics 2014; 11(4): 817-39.
[http://dx.doi.org/10.1007/s13311-014-0299-5] [PMID: 25159276]
[9]
Hwu W-L, Muramatsu S, Tseng S-H, et al. Gene therapy for aromatic l-amino acid decarboxylase deficiency. Sci Transl Med 2012; 4: 134-61.
[http://dx.doi.org/10.1126/scitranslmed.3003640]
[10]
Sehara Y, Fujimoto KI, Ikeguchi K, et al. Persistent expression of dopamine-synthesizing enzymes 15 years after gene transfer in a primate model of parkinson’s disease. Hum Gene Ther Clin Dev 2017; 28(2): 74-9.
[http://dx.doi.org/10.1089/humc.2017.010] [PMID: 28279081]
[11]
Mittermeyer G, Christine CW, Rosenbluth KH, et al. Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson’s disease. Hum Gene Ther 2012; 23(4): 377-81.
[http://dx.doi.org/10.1089/hum.2011.220] [PMID: 22424171]
[12]
Murphy SR, Chang CCY, Dogbevia G, et al. Acat1 knockdown gene therapy decreases amyloid-β in a mouse model of Alzheimer’s disease. Mol Ther 2013; 21(8): 1497-506.
[http://dx.doi.org/10.1038/mt.2013.118] [PMID: 23774792]
[13]
Sudhakar V, Richardson RM. Gene therapy for neurodegenerative diseases. Neurotherapeutics 2019; 16(1): 166-75.
[http://dx.doi.org/10.1007/s13311-018-00694-0] [PMID: 30542906]
[14]
Brain Basics NIH. Genes at work in the brain| national institute of neurological disorders and stroke. Available at https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Genes-Work-Brain
[15]
Harilal S, Jose J, Parambi DGT, et al. Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules. Brain Res Bull 2020; 160: 121-40.
[http://dx.doi.org/10.1016/j.brainresbull.2020.03.018] [PMID: 32315731]
[16]
Deverman BE, Ravina BM, Bankiewicz KS, Paul SM, Sah DWY. Gene therapy for neurological disorders: progress and prospects. Nat Rev Drug Discov 2018; 17(9): 641-59.
[http://dx.doi.org/10.1038/nrd.2018.110] [PMID: 30093643]
[17]
Foust KD, Wang X, McGovern VL, et al. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol 2010; 28(3): 271-4.
[http://dx.doi.org/10.1038/nbt.1610] [PMID: 20190738]
[18]
Murrey DA, Naughton BJ, Duncan FJ, et al. Feasibility and safety of systemic rAAV9-hNAGLU delivery for treating mucopolysaccharidosis IIIB: toxicology, biodistribution, and immunological assessments in primates. Hum Gene Ther Clin Dev 2014; 25(2): 72-84.
[http://dx.doi.org/10.1089/humc.2013.208] [PMID: 24720466]
[19]
Mattar CN, Waddington SN, Biswas A, et al. Systemic delivery of scAAV9 in fetal macaques facilitates neuronal transduction of the central and peripheral nervous systems. Gene Ther 2013; 20(1): 69-83.
[http://dx.doi.org/10.1038/gt.2011.216] [PMID: 22278413]
[20]
Choudhury SR, Fitzpatrick Z, Harris AF, et al. In vivo selection yields AAV-B1 capsid for central nervous system and muscle gene therapy. Mol Ther 2016; 24(7): 1247-57.
[http://dx.doi.org/10.1038/mt.2016.84] [PMID: 27117222]
[21]
Choudhury SR, Harris AF, Cabral DJ, et al. Widespread central nervous system gene transfer and silencing after systemic delivery of novel AAV-AS vector. Mol Ther 2016; 24(4): 726-35.
[http://dx.doi.org/10.1038/mt.2015.231] [PMID: 26708003]
[22]
Tardieu M, Zérah M, Gougeon M-L, et al. Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial. Lancet Neurol 2017; 16(9): 712-20.
[http://dx.doi.org/10.1016/S1474-4422(17)30169-2] [PMID: 28713035]
[23]
Weinberg MS, Samulski RJ, McCown TJ. Adeno-associated virus (AAV) gene therapy for neurological disease. Neuropharmacology 2013; 69: 82-8.
[http://dx.doi.org/10.1016/j.neuropharm.2012.03.004] [PMID: 22465202]
[24]
Cearley CN, Wolfe JH. A single injection of an adeno-associated virus vector into nuclei with divergent connections results in widespread vector distribution in the brain and global correction of a neurogenetic disease. J Neurosci 2007; 27(37): 9928-40.
[http://dx.doi.org/10.1523/JNEUROSCI.2185-07.2007] [PMID: 17855607]
[25]
Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med 2017; 377(18): 1713-22.
[http://dx.doi.org/10.1056/NEJMoa1706198] [PMID: 29091557]
[26]
Barkats M, Bilang-Bleuel A, Buc-Caron MH, et al. Adenovirus in the brain: recent advances of gene therapy for neurodegenerative diseases. Prog Neurobiol 1998; 55(4): 333-41.
[http://dx.doi.org/10.1016/S0301-0082(98)00028-8] [PMID: 9654383]
[27]
Lombardo A, Genovese P, Beausejour CM, et al. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol 2007; 25(11): 1298-306.
[http://dx.doi.org/10.1038/nbt1353] [PMID: 17965707]
[28]
Milone MC, O’Doherty U. Clinical use of lentiviral vectors. Leukemia 2018; 32(7): 1529-41.
[http://dx.doi.org/10.1038/s41375-018-0106-0] [PMID: 29654266]
[29]
Yee JK, Miyanohara A, LaPorte P, Bouic K, Burns JC, Friedmann T. A general method for the generation of high-titer, pantropic retroviral vectors: highly efficient infection of primary hepatocytes. Proc Natl Acad Sci USA 1994; 91(20): 9564-8.
[http://dx.doi.org/10.1073/pnas.91.20.9564] [PMID: 7937806]
[30]
Aiken C. Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A. J Virol 1997; 71(8): 5871-7.
[http://dx.doi.org/10.1128/JVI.71.8.5871-5877.1997] [PMID: 9223476]
[31]
Maurice M, Verhoeyen E, Salmon P, Trono D, Russell SJ, Cosset F-L. Efficient gene transfer into human primary blood lymphocytes by surface-engineered lentiviral vectors that display a T cell-activating polypeptide. Blood 2002; 99(7): 2342-50.
[http://dx.doi.org/10.1182/blood.V99.7.2342] [PMID: 11895766]
[32]
Sinclair AM, Agrawal YP, Elbar E, Agrawal R, Ho AD, Levine F. Interaction of vesicular stomatitis virus-G pseudotyped retrovirus with CD34+ and CD34+ CD38- hematopoietic progenitor cells. Gene Ther 1997; 4(9): 918-27.
[http://dx.doi.org/10.1038/sj.gt.3300479] [PMID: 9349428]
[33]
Verhoeyen E, Dardalhon V, Ducrey-Rundquist O, Trono D, Taylor N, Cosset F-L. IL-7 surface-engineered lentiviral vectors promote survival and efficient gene transfer in resting primary T lymphocytes. Blood 2003; 101(6): 2167-74.
[http://dx.doi.org/10.1182/blood-2002-07-2224] [PMID: 12446448]
[34]
Azzouz M, Martin-Rendon E, Barber RD, 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): 10302-12.
[http://dx.doi.org/10.1523/JNEUROSCI.22-23-10302.2002] [PMID: 12451130]
[35]
Jarraya B, Boulet S, Ralph GS, et al. Dopamine gene therapy for parkinson’s disease in a nonhuman primate without associated dyskinesia. Sci Transl Med 2009; 1: 2-4.
[http://dx.doi.org/10.1126/scitranslmed.3000130]
[36]
Palfi S, Gurruchaga JM, Ralph GS, et al. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: a dose escalation, open-label, phase 1/2 trial. Lancet 2014; 383(9923): 1138-46.
[http://dx.doi.org/10.1016/S0140-6736(13)61939-X] [PMID: 24412048]
[37]
Katsouri L, Lim YM, Blondrath K, et al. PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer’s disease model. Proc Natl Acad Sci USA 2016; 113(43): 12292-7.
[http://dx.doi.org/10.1073/pnas.1606171113] [PMID: 27791018]
[38]
Palfi S, Gurruchaga JM, Lepetit H, et al. Long-term follow-up of a phase I/II study of ProSavin, a lentiviral vector gene therapy for Parkinson’s disease. Hum Gene Ther Clin Dev 2018; 29(3): 148-55.
[http://dx.doi.org/10.1089/humc.2018.081] [PMID: 30156440]
[39]
Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet 2003; 4(5): 346-58.
[http://dx.doi.org/10.1038/nrg1066] [PMID: 12728277]
[40]
Marconi P, Simonato M, Zucchini S, et al. Replication-defective herpes simplex virus vectors for neurotrophic factor gene transfer in vitro and in vivo. Gene Ther 1999; 6(5): 904-12.
[http://dx.doi.org/10.1038/sj.gt.3300882] [PMID: 10505116]
[41]
Krisky DM, Wolfe D, Goins WF, et al. Deletion of multiple immediate-early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Ther 1998; 5(12): 1593-603.
[http://dx.doi.org/10.1038/sj.gt.3300766] [PMID: 10023438]
[42]
Shepard AA, DeLuca NA. A second-site revertant of a defective herpes simplex virus ICP4 protein with restored regulatory activities and impaired DNA-binding properties. J Virol 1991; 65(2): 787-95.
[http://dx.doi.org/10.1128/JVI.65.2.787-795.1991] [PMID: 1846199]
[43]
Wu N, Watkins SC, Schaffer PA, DeLuca NA. Prolonged gene expression and cell survival after infection by a herpes simplex virus mutant defective in the immediate-early genes encoding ICP4, ICP27, and ICP22. J Virol 1996; 70(9): 6358-69.
[http://dx.doi.org/10.1128/JVI.70.9.6358-6369.1996] [PMID: 8709264]
[44]
Samaniego LA, Wu N, DeLuca NA. The herpes simplex virus immediate-early protein ICP0 affects transcription from the viral genome and infected-cell survival in the absence of ICP4 and ICP27. J Virol 1997; 71(6): 4614-25.
[http://dx.doi.org/10.1128/JVI.71.6.4614-4625.1997] [PMID: 9151855]
[45]
Bloom DC, Giordani NV, Kwiatkowski DL. Epigenetic regulation of latent HSV-1 gene expression. Biochim Biophys Acta 2010; 1799(3-4): 246-56.
[http://dx.doi.org/10.1016/j.bbagrm.2009.12.001] [PMID: 20045093]
[46]
Miyagawa Y, Marino P, Verlengia G, et al. Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity. Proc Natl Acad Sci USA 2015; 112(13): E1632-41.
[http://dx.doi.org/10.1073/pnas.1423556112] [PMID: 25775541]
[47]
Verlengia G, Miyagawa Y, Ingusci S, Cohen JB, Simonato M, Glorioso JC. Engineered HSV vector achieves safe long-term transgene expression in the central nervous system. Sci Rep 2017; 7(1): 1507.
[http://dx.doi.org/10.1038/s41598-017-01635-1] [PMID: 28473703]
[48]
Baum C, Kustikova O, Modlich U, Li Z, Fehse B. Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors. Hum Gene Ther 2006; 17(3): 253-63.
[http://dx.doi.org/10.1089/hum.2006.17.253] [PMID: 16544975]
[49]
Bessis N. GarciaCozar FJ, Boissier MC. Immune responses to gene therapy vectors: influence on vector function and effector mechanisms. Gene Ther 2004; 11(Suppl. 1): S10-7.
[http://dx.doi.org/10.1038/sj.gt.3302364] [PMID: 15454952]
[50]
Bouard D, Alazard-Dany D, Cosset FL. Viral vectors: from virology to transgene expression. Br J Pharmacol 2009; 157(2): 153-65.
[http://dx.doi.org/10.1038/bjp.2008.349] [PMID: 18776913]
[51]
Waehler R, Russell SJ, Curiel DT. Engineering targeted viral vectors for gene therapy. Nat Rev Genet 2007; 8(8): 573-87.
[http://dx.doi.org/10.1038/nrg2141] [PMID: 17607305]
[52]
Buck J, Grossen P, Cullis PR, Huwyler J, Witzigmann D. Lipid-based dna therapeutics: hallmarks of non-viral gene delivery. ACS Nano 2019; 13(4): 3754-82.
[http://dx.doi.org/10.1021/acsnano.8b07858] [PMID: 30908008]
[53]
Mintzer MA, Simanek EE. Nonviral vectors for gene delivery. Chem Rev 2009; 109(2): 259-302.
[http://dx.doi.org/10.1021/cr800409e] [PMID: 19053809]
[54]
Pack DW, Hoffman AS, Pun S, Stayton PS. Design and development of polymers for gene delivery. Nat Rev Drug Discov 2005; 4(7): 581-93.
[http://dx.doi.org/10.1038/nrd1775] [PMID: 16052241]
[55]
Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet 2014; 15(8): 541-55.
[http://dx.doi.org/10.1038/nrg3763] [PMID: 25022906]
[56]
Li W, Szoka FC Jr. Lipid-based nanoparticles for nucleic acid delivery. Pharm Res 2007; 24(3): 438-49.
[http://dx.doi.org/10.1007/s11095-006-9180-5] [PMID: 17252188]
[57]
Conceição M, Mendonça L, Nóbrega C, et al. Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype. Biomaterials 2016; 82: 124-37.
[http://dx.doi.org/10.1016/j.biomaterials.2015.12.021] [PMID: 26757259]
[58]
Carradori D, Eyer J, Saulnier P, Préat V, des Rieux A. The therapeutic contribution of nanomedicine to treat neurodegenerative diseases via neural stem cell differentiation. Biomaterials 2017; 123: 77-91.
[http://dx.doi.org/10.1016/j.biomaterials.2017.01.032] [PMID: 28161683]
[59]
Kojima R, Bojar D, Rizzi G, et al. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat Commun 2018; 9(1): 1305.
[http://dx.doi.org/10.1038/s41467-018-03733-8] [PMID: 29610454]
[60]
Niu S, Zhang L-K, Zhang L, et al. Inhibition by multifunctional magnetic nanoparticles loaded with alpha-synuclein RNAi plasmid in a parkinson’s disease model. Theranostics 2017; 7(2): 344-56.
[http://dx.doi.org/10.7150/thno.16562] [PMID: 28042339]
[61]
Semple SC, Akinc A, Chen J, et al. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 2010; 28(2): 172-6.
[http://dx.doi.org/10.1038/nbt.1602] [PMID: 20081866]
[62]
Kattenhorn LM, Tipper CH, Stoica L, et al. Adeno-associated virus gene therapy for liver disease. Hum Gene Ther 2016; 27(12): 947-61.
[http://dx.doi.org/10.1089/hum.2016.160] [PMID: 27897038]
[63]
Federici T, Taub JS, Baum GR, et al. Robust spinal motor neuron transduction following intrathecal delivery of AAV9 in pigs. Gene Ther 2012; 19(8): 852-9.
[http://dx.doi.org/10.1038/gt.2011.130] [PMID: 21918551]
[64]
Hinderer C, Bell P, Katz N, et al. Evaluation of intrathecal routes of administration for adeno-associated viral vectors in large animals. Hum Gene Ther 2018; 29(1): 15-24.
[http://dx.doi.org/10.1089/hum.2017.026] [PMID: 28806897]
[65]
Hinderer C, Bell P, Gurda BL, et al. Intrathecal gene therapy corrects CNS pathology in a feline model of mucopolysaccharidosis I. Mol Ther 2014; 22(12): 2018-27.
[http://dx.doi.org/10.1038/mt.2014.135] [PMID: 25027660]
[66]
Samaranch L, Salegio EA, San Sebastian W, et al. Adeno-associated virus serotype 9 transduction in the central nervous system of nonhuman primates. Hum Gene Ther 2012; 23(4): 382-9.
[http://dx.doi.org/10.1089/hum.2011.200] [PMID: 22201473]
[67]
Armbruster N, Lattanzi A, Jeavons M, et al. Efficacy and biodistribution analysis of intracerebroventricular administration of an optimized scAAV9-SMN1 vector in a mouse model of spinal muscular atrophy. Mol Ther Methods Clin Dev 2016; 3: 16060.
[http://dx.doi.org/10.1038/mtm.2016.60] [PMID: 27652289]
[68]
Dirren E, Aebischer J, Rochat C, Towne C, Schneider BL, Aebischer P. SOD1 silencing in motoneurons or glia rescues neuromuscular function in ALS mice. Ann Clin Transl Neurol 2015; 2(2): 167-84.
[http://dx.doi.org/10.1002/acn3.162] [PMID: 25750921]
[69]
Levites Y, Jansen K, Smithson LA, et al. Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid β, amyloid β40, and amyloid β42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice. J Neurosci 2006; 26(46): 11923-8.
[http://dx.doi.org/10.1523/JNEUROSCI.2795-06.2006] [PMID: 17108166]
[70]
Ahmed SG, Waddington SN, Boza-Morán MG, Yáñez-Muñoz RJ. High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors. J Control Release 2018; 273: 99-107.
[http://dx.doi.org/10.1016/j.jconrel.2017.12.029] [PMID: 29289570]
[71]
Miyanohara A, Kamizato K, Juhas S, et al. Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs. Mol Ther Methods Clin Dev 2016; 3: 16046.
[http://dx.doi.org/10.1038/mtm.2016.46] [PMID: 27462649]
[72]
Biferi MG, Cohen-Tannoudji M, Cappelletto A, et al. A New AAV10-U7-mediated gene therapy prolongs survival and restores function in an ALS mouse model. Mol Ther 2017; 25(9): 2038-52.
[http://dx.doi.org/10.1016/j.ymthe.2017.05.017] [PMID: 28663100]
[73]
ClinicalTrials.gov. Randomized, controlled study evaluating CERE-110 in subjects with mild to moderate Alzheimer’s disease Available at https://clinicaltrials.gov/ct2/show/NCT00876863
[74]
ClinicalTrials.gov. Safety and Efficacy Study of VY-AADC01 for advanced Parkinson’s disease Available at https://clinicaltrials.gov/ct2/show/NCT03065192
[75]
ClinicalTrials.gov. AAV2-GDNF for advanced Parkinson’s disease. Available at. https://clinicaltrials.gov/ct2/show/NCT01621581
[76]
ClinicalTrials.gov. AADC Gene therapy for Parkinson’s disease Available at https://clinicaltrials.gov/ct2/show/NCT02418598
[77]
ClinicalTrials.gov. Double-Blind, multicenter, sham surgery controlled study of CERE-120 in subjects with idiopathic Parkinson’s disease Available at https://clinicaltrials.gov/ct2/show/NCT00400634
[78]
ClinicalTrials.gov. Phase I/ii study of the safety, efficacy and dose evaluation of prosavin for the treatment of bilateral idiopathic Parkinson’s disease. Available at. https://clinicaltrials.gov/ct2/show/NCT00627588
[79]
ClinicalTrials.gov. Study of AAV-GAD gene transfer into the subthalamic nucleus for Parkinson’s disease Available at https://clinicaltrials.gov/ct2/show/NCT00643890
[80]
ClinicalTrials.gov. Safety, tolerability, pharmacokinetics, and pharmacodynamics of ISIS 443139 in participants with early manifest Huntington’s disease Available at https://clinicaltrials.gov/ct2/show/NCT02519036
[81]
ClinicalTrials.gov. Safety and tolerability of WVE-120101 in patients with Huntington’s disease Available at https://clinicaltrials.gov/ct2/show/NCT03225833
[82]
ClinicalTrials.gov. Safety, tolerability, and activity study of ISIS SOD1Rx to treat familial amyotrophic lateral sclerosis (ALS) caused by SOD1 gene mutations. Available at . https://clinicaltrials.gov/ct2/show/NCT01041222
[83]
ClinicalTrials.gov. Intracerebral gene therapy for children with early onset forms of metachromatic leukodystrophy Available at https://clinicaltrials.gov/ct2/show/NCT01801709
[84]
ClinicalTrials.gov. Re-administration of intramuscular AAV9 in patients with late-onset Pompe disease Available at https://clinicaltrials.gov/ct2/show/NCT02240407
[85]
ClinicalTrials.gov. Safety study of recombinant adeno-associated virus acid alpha-glucosidase to treat Pompe disease Available at https://clinicaltrials.gov/ct2/show/NCT00976352
[86]
ClinicalTrials.gov. Gene transfer clinical trial for spinal muscular atrophy type 1. Available at . https://clinicaltrials.gov/ct2/show/NCT02122952
[87]
ClinicalTrials.gov. A Study to assess the efficacy and safety of nusinersen (ISIS 396443) in participants with later-onset spinal muscular atrophy (SMA). Available at. https://clinicaltrials.gov/ct2/show/NCT02292537
[88]
Hudry E, Vandenberghe LH. Therapeutic AAV gene transfer to the nervous system: a clinical reality. Neuron 2019; 101(5): 839-62.
[http://dx.doi.org/10.1016/j.neuron.2019.02.017] [PMID: 30844402]
[89]
Hinderer C, Katz N, Buza EL, et al. Severe toxicity in nonhuman primates and piglets following high-dose intravenous administration of an adeno-associated virus vector expressing human SMN. Hum Gene Ther 2018; 29(3): 285-98.
[http://dx.doi.org/10.1089/hum.2018.015] [PMID: 29378426]
[90]
Vandamme C, Adjali O, Mingozzi F. Unraveling the complex story of immune responses to AAV vectors trial after trial. Hum Gene Ther 2017; 28(11): 1061-74.
[http://dx.doi.org/10.1089/hum.2017.150] [PMID: 28835127]
[91]
Amado D, Mingozzi F, Hui D, et al. Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness. Sci Transl Med 2010; 221ra16
[http://dx.doi.org/10.1126/scitranslmed.3000659]
[92]
Chandler RJ, Sands MS, Venditti CP. Recombinant adeno-associated viral integration and genotoxicity: insights from animal models. Hum Gene Ther 2017; 28(4): 314-22.
[http://dx.doi.org/10.1089/hum.2017.009] [PMID: 28293963]
[93]
Gil-Farina I, Fronza R, Kaeppel C, et al. Recombinant AAV integration is not associated with hepatic genotoxicity in nonhuman primates and patients. Mol Ther 2016; 24(6): 1100-5.
[http://dx.doi.org/10.1038/mt.2016.52] [PMID: 26948440]

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