Login Register Cart 0
Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Review Article

Translational Approach using Advanced Therapy Medicinal Products for Huntington's Disease

Author(s): Maryam Alsadat Mousavi, Maliheh Rezaei, Mahsa Pourhamzeh, Mehri Salari, Nikoo Hossein-Khannazer, Anastasia Shpichka, Seyed Massood Nabavi, Peter Timashev* and Massoud Vosough*

Volume 20, Issue 1, 2025

Published on: 23 May, 2024

Page: [14 - 31] Pages: 18

DOI: 10.2174/0127724328300166240510071548

Price: $65

Abstract

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed.

Keywords: Advanced therapy medicinal products, ATMP, huntington's disease, cell therapy, gene therapy, RNAs.

« Previous Next »
Graphical Abstract

[1]
Wexler A, Wild EJ, Tabrizi SJ. George Huntington: A legacy of inquiry, empathy and hope. Brain 2016; 139(8): 2326-33.
[http://dx.doi.org/10.1093/brain/aww165] [PMID: 27421790]
[2]
Rawlins MD, Wexler NS, Wexler AR, et al. The prevalence of Huntington’s Disease. Neuroepidemiology 2016; 46(2): 144-53.
[http://dx.doi.org/10.1159/000443738] [PMID: 26824438]
[3]
Barker RA, Fujimaki M, Rogers P, Rubinsztein DC. Huntingtin-lowering strategies for Huntington’s disease. Expert Opin Investig Drugs 2020; 29(10): 1125-32.
[http://dx.doi.org/10.1080/13543784.2020.1804552] [PMID: 32745442]
[4]
van Duijn E, Fernandes AR, Abreu D, Ware JJ, Neacy E, Sampaio C. Incidence of completed suicide and suicide attempts in a global prospective study of Huntington’s disease. BJPsych Open 2021; 7(5): e158.
[http://dx.doi.org/10.1192/bjo.2021.969]
[5]
European Medicines Agency Advanced therapy medicinal products 2017. Available From: https://www.ema.europa.eu/en/human-regulatory-overview/advanced-therapy-medicinal-productsoverview
[6]
Galli MC. ATMPs for Cancer immunotherapy: A regulatory overview. Methods Mol Biol 2016; 1393: 1-9.
[http://dx.doi.org/10.1007/978-1-4939-3338-9_1] [PMID: 27033211]
[7]
Hossein-Khannazer N, Vosough M, Salahi S, Mousavi MA, Azizi G. Stem cell-based and advanced therapeutic modalities for Parkinson’s disease: A risk-effectiveness patient-centered analysis. Curr Neuropharmacol 2022; 20(12): 2320-45.
[http://dx.doi.org/10.2174/1570159X20666220201100238] [PMID: 35105291]
[8]
Meij P, Canals JM, Lowery M, Scott M. Advanced therapy medicinal products. Leuven, Belgium: LERU 2019.
[9]
Kay C, Hayden MR, Leavitt BR. Epidemiology of huntington disease. Handb Clin Neurol 2017; 144: 31-46.
[http://dx.doi.org/10.1016/B978-0-12-801893-4.00003-1] [PMID: 28947124]
[10]
Paradisi I. Hernández A, Arias S. Huntington disease mutation in Venezuela: Age of onset, haplotype analyses and geographic aggregation. J Hum Genet 2008; 53(2): 127-35.
[http://dx.doi.org/10.1007/s10038-007-0227-1] [PMID: 18157708]
[11]
Medina A, Mahjoub Y, Shaver L, Pringsheim T. Prevalence and incidence of Huntington’s disease: An updated systematic review and meta‐analysis. Mov Disord 2022; 37(12): 2327-35.
[http://dx.doi.org/10.1002/mds.29228] [PMID: 36161673]
[12]
Baig SS, Strong M, Quarrell OWJ. The global prevalence of Huntington’s disease: A systematic review and discussion. Neurodegener Dis Manag 2016; 6(4): 331-43.
[http://dx.doi.org/10.2217/nmt-2016-0008] [PMID: 27507223]
[13]
Walker FO. Huntington’s disease. Lancet 2007; 369(9557): 218-28.
[http://dx.doi.org/10.1016/S0140-6736(07)60111-1] [PMID: 17240289]
[14]
Young AB. Huntingtin in health and disease. J Clin Invest 2003; 111(3): 299-302.
[http://dx.doi.org/10.1172/JCI17742] [PMID: 12569151]
[15]
Wanker EE, Ast A, Schindler F, Trepte P, Schnoegl S. The pathobiology of perturbed mutant huntingtin protein–protein interactions in Huntington’s disease. J Neurochem 2019; 151(4): 507-19.
[http://dx.doi.org/10.1111/jnc.14853] [PMID: 31418858]
[16]
Tabrizi SJ, Flower MD, Ross CA, Wild EJ. Huntington disease: New insights into molecular pathogenesis and therapeutic opportunities. Nat Rev Neurol 2020; 16(10): 529-46.
[http://dx.doi.org/10.1038/s41582-020-0389-4] [PMID: 32796930]
[17]
Dong X, Zong S, Witting A, Lindenberg KS, Kochanek S, Huang B. Adenovirus vector‐based in vitro neuronal cell model for Huntington’s disease with human disease‐like differential aggregation and degeneration. J Gene Med 2012; 14(7): 468-81.
[http://dx.doi.org/10.1002/jgm.2641] [PMID: 22700462]
[18]
Pandey M, Rajamma U. Huntington’s disease: The coming of age. J Genet 2018; 97(3): 649-64.
[http://dx.doi.org/10.1007/s12041-018-0957-1] [PMID: 30027901]
[19]
Lipe H, Bird T. Late onset Huntington Disease: Clinical and genetic characteristics of 34 cases. J Neurol Sci 2009; 276(1-2): 159-62.
[20]
Frank S. Treatment of Huntington’s disease. Neurotherapeutics 2014; 11(1): 153-60.
[http://dx.doi.org/10.1007/s13311-013-0244-z] [PMID: 24366610]
[21]
Dickey AS, La Spada AR. Therapy development in Huntington disease: From current strategies to emerging opportunities. Am J Med Genet A 2018; 176(4): 842-61.
[http://dx.doi.org/10.1002/ajmg.a.38494] [PMID: 29218782]
[22]
Kumar A, Kumar V, Singh K, et al. Therapeutic advances for Huntington’s disease. Brain Sci 2020; 10(1): 43.
[http://dx.doi.org/10.3390/brainsci10010043] [PMID: 31940909]
[23]
Stahl CM, Feigin A. Medical, surgical, and genetic treatment of Huntington disease. Neurol Clin 2020; 38(2): 367-78.
[http://dx.doi.org/10.1016/j.ncl.2020.01.010] [PMID: 32279715]
[24]
Kim A, Lalonde K, Truesdell A, et al. New avenues for the treatment of Huntington’s disease. Int J Mol Sci 2021; 22(16): 8363.
[http://dx.doi.org/10.3390/ijms22168363] [PMID: 34445070]
[25]
Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C. Therapeutic interventions for disease progression in Huntington’s disease. Cochrane Database Syst Rev 2009; 2009(3): CD006455.
[http://dx.doi.org/10.1002/14651858.CD006455.pub2]
[26]
Venuto CS, McGarry A, Ma Q, Kieburtz K. Pharmacologic approaches to the treatment of Huntington’s disease. Mov Disord 2012; 27(1): 31-41.
[http://dx.doi.org/10.1002/mds.23953] [PMID: 21997232]
[27]
Jankovic J, Clarence-Smith K. Tetrabenazine for the treatment of chorea and other hyperkinetic movement disorders. Expert Rev Neurother 2011; 11(11): 1509-23.
[http://dx.doi.org/10.1586/ern.11.149] [PMID: 22014129]
[28]
Wyant KJ, Ridder AJ, Dayalu P. Huntington’s disease—update on treatments. Curr Neurol Neurosci Rep 2017; 17(4): 33.
[http://dx.doi.org/10.1007/s11910-017-0739-9] [PMID: 28324302]
[29]
Frank S. Effect of Deutetrabenazine on chorea among patients with huntington disease a randomized clinical trial. JAMA 2016; 316(1): 40-50.
[30]
Claassen DO, Carroll B, De Boer LM, et al. Indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease. J Clin Mov Disord 2017; 4(1): 3.
[http://dx.doi.org/10.1186/s40734-017-0051-5] [PMID: 28265459]
[31]
Loy C, Claassen DO, Colcher A, Davis CS, Duker A, Eberly SW. Safety of converting from tetrabenazine to deutetrabenazine for the treatment of Chorea. JAMA Neurol 2017; 74(8): 977-82.
[32]
Furr Stimming E, Claassen DO, Kayson E, et al. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington’s disease (KINECT-HD): A phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2023; 22(6): 494-504.
[http://dx.doi.org/10.1016/S1474-4422(23)00127-8] [PMID: 37210099]
[33]
Burgunder JM, Guttman M, Perlman S, Goodman N, van Kammen DP, Goodman L. An international survey-based algorithm for the pharmacologic treatment of chorea in Huntington’s disease. PLoS Curr 2011; 3: RRN1260.
[http://dx.doi.org/10.1371/currents.RRN1260] [PMID: 21975581]
[34]
Armstrong MJ. Evidence-based guideline: Pharmacologic treatment of chorea in Huntington disease. Neurology 2012; 793(6): 597-603.
[35]
Coppen EM, Roos RAC. Current pharmacological approaches to reduce chorea in Huntington’s disease. Drugs 2017; 77(1): 29-46.
[http://dx.doi.org/10.1007/s40265-016-0670-4] [PMID: 27988871]
[36]
Dallocchio C, Buffa C, Tinelli C, Mazzarello P. Effectiveness of risperidone in Huntington chorea patients. J Clin Psychopharmacol 1999; 19(1): 101-3.
[http://dx.doi.org/10.1097/00004714-199902000-00020] [PMID: 9934953]
[37]
Priller J, Ecker D, Landwehrmeyer B, Craufurd D. A Europe‐wide assessment of current medication choices in Huntington’s disease. Mov Disord 2008; 23(12): 1788.
[http://dx.doi.org/10.1002/mds.22188] [PMID: 18649399]
[38]
Lucetti C, Gambaccini G, Bernardini S, et al. Amantadine in Huntington’s disease: Open-label video-blinded study. Neurol Sci 2002; 23(0) (Suppl. 2): s83-4.
[http://dx.doi.org/10.1007/s100720200081] [PMID: 12548355]
[39]
Huntington Study Group. Dosage effects of riluzole in Huntington’s disease. Neurology 2003; 61(11): 1551-6.
[http://dx.doi.org/10.1212/01.WNL.0000096019.71649.2B] [PMID: 14663041]
[40]
Landwehrmeyer GB, Dubois B, de Yébenes JG, et al. Riluzole in Huntington’s disease: A 3‐year, randomized controlled study. Ann Neurol 2007; 62(3): 262-72.
[http://dx.doi.org/10.1002/ana.21181] [PMID: 17702031]
[41]
O’Suilleabhain P, Dewey RB Jr. A randomized trial of amantadine in Huntington disease. Arch Neurol 2003; 60(7): 996-8.
[http://dx.doi.org/10.1001/archneur.60.7.996] [PMID: 12873857]
[42]
Testa CM, Jankovic J. Huntington disease: A quarter century of progress since the gene discovery. J Neurol Sci 2019; 396: 52-68.
[http://dx.doi.org/10.1016/j.jns.2018.09.022] [PMID: 30419368]
[43]
Paulsen JS, Butters N, Sadek JR, et al. Distinct cognitive profiles of cortical and subcortical dementia in advanced illness. Neurology 1995; 45(5): 951-6.
[http://dx.doi.org/10.1212/WNL.45.5.951] [PMID: 7746413]
[44]
Fernandez HH, Friedman JH, Grace J, Beason-Hazen S. Donepezil for Huntington’s disease. Mov Disord 2000; 15(1): 173-6.
[http://dx.doi.org/10.1002/1531-8257(200001)15:1<173::AID-MDS1032>3.0.CO;2-T] [PMID: 10634264]
[45]
Rot U, Kobal J, Sever A. Pirtošek Z, Mesec A. Rivastigmine in the treatment of Huntington’s disease. Eur J Neurol 2002; 9(6): 689-90.
[http://dx.doi.org/10.1046/j.1468-1331.2002.00447_4.x] [PMID: 12453090]
[46]
de Tommaso M, Specchio N, Sciruicchio V, Difruscolo O, Specchio LM. Effects of rivastigmine on motor and cognitive impairment in Huntington’s disease. Mov Disord 2004; 19(12): 1516-8.
[http://dx.doi.org/10.1002/mds.20235] [PMID: 15390067]
[47]
Petrikis P, Andreou C, Piachas A, Bozikas VP, Karavatos A. Treatment of Huntington??s disease with galantamine. Int Clin Psychopharmacol 2004; 19(1): 49-50.
[http://dx.doi.org/10.1097/00004850-200401000-00010] [PMID: 15101572]
[48]
Galts CPC, Bettio LEB, Jewett DC, et al. Depression in neurodegenerative diseases: Common mechanisms and current treatment options. Neurosci Biobehav Rev 2019; 102: 56-84.
[http://dx.doi.org/10.1016/j.neubiorev.2019.04.002] [PMID: 30995512]
[49]
van Duijn E. Medical treatment of behavioral manifestations of Huntington disease. Handb Clin Neurol 2017; 144: 129-39.
[http://dx.doi.org/10.1016/B978-0-12-801893-4.00011-0] [PMID: 28947111]
[50]
Moulton CD, Hopkins CWP, Bevan-Jones WR. Systematic review of pharmacological treatments for depressive symptoms in Huntington’s disease. Mov Disord 2014; 29(12): 1556-61.
[http://dx.doi.org/10.1002/mds.25980] [PMID: 25111961]
[51]
Paleacu D, Anca M, Giladi N. Olanzapine in Huntington’s disease. Acta Neurol Scand 2002; 105(6): 441-4.
[http://dx.doi.org/10.1034/j.1600-0404.2002.01197.x] [PMID: 12027832]
[52]
Nasrallah HA, Black DW, Goldberg JF, Muzina DJ, Pariser SF. Diagnosing and managing psychotic and mood disorders. Ann Clin Psychiatry 2008; 20 (Suppl. 1): S1-S28.
[PMID: 19034748]
[53]
Eddy CM, Parkinson EG, Rickards HE. Changes in mental state and behaviour in Huntington’s disease. Lancet Psychiatry 2016; 3(11): 1079-86.
[http://dx.doi.org/10.1016/S2215-0366(16)30144-4] [PMID: 27663851]
[54]
Anderson KE, van Duijn E, Craufurd D, et al. Clinical management of neuropsychiatric symptoms of Huntington disease: Expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders. J Huntingtons Dis 2018; 7(4): 355-66.
[http://dx.doi.org/10.3233/JHD-180293] [PMID: 30040737]
[55]
van Duijn E, Kingma EM, van der Mast RC. Psychopathology in verified Huntington’s disease gene carriers. J Neuropsychiatry Clin Neurosci 2007; 19(4): 441-8.
[http://dx.doi.org/10.1176/jnp.2007.19.4.441] [PMID: 18070848]
[56]
van Duijn E, Craufurd D, Hubers AAM, et al. Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY). J Neurol Neurosurg Psychiatry 2014; 85(12): 1411-8.
[http://dx.doi.org/10.1136/jnnp-2013-307343] [PMID: 24828898]
[57]
Khodagholi F, Maleki A, Motamedi F, Mousavi MA, Rafiei S, Moslemi M. Oxytocin prevents the development of 3-NP-induced anxiety and depression in male and female rats: Possible interaction of OXTR and mGluR2. Cell Mol Neurobiol 2022; 42(4): 1105-23.
[http://dx.doi.org/10.1007/s10571-020-01003-0] [PMID: 33201416]
[58]
Simmons DA, Massa SM. Neurotrophin receptor signaling as a therapeutic target for Huntington’s Disease. CNS Neurol Disord Drug Targets 2017; 16(3): 291-302.
[59]
Devadiga SJ, Bharate SS. Recent developments in the management of Huntington’s disease. Bioorg Chem 2022; 120: 105642.
[http://dx.doi.org/10.1016/j.bioorg.2022.105642] [PMID: 35121553]
[60]
Wheelock VL, Tempkin T, Marder K, et al. Predictors of nursing home placement in Huntington disease. Neurology 2003; 60(6): 998-1001.
[http://dx.doi.org/10.1212/01.WNL.0000052992.58107.67] [PMID: 12654967]
[61]
Vuong K, Canning CG, Menant JC, Loy CT. Gait, balance, and falls in Huntington disease. Handb Clin Neurol 2018; 159: 251-60.
[http://dx.doi.org/10.1016/B978-0-444-63916-5.00016-1] [PMID: 30482318]
[62]
Bohlen S, Ekwall C. Hellström K, et al. Physical therapy in H untington’s disease – toward objective assessments? Eur J Neurol 2013; 20(2): 389-93.
[http://dx.doi.org/10.1111/j.1468-1331.2012.03760.x] [PMID: 22672573]
[63]
Hartmann CJ, Groiss SJ, Vesper J, Schnitzler A, Wojtecki L. Brain stimulation in Huntington’s disease. Neurodegener Dis Manag 2016; 6(3): 223-36.
[http://dx.doi.org/10.2217/nmt-2016-0007] [PMID: 27230813]
[64]
Gonzalez V, Cif L, Biolsi B, et al. Deep brain stimulation for Huntington’s disease: Long-term results of a prospective open-label study. J Neurosurg 2014; 121(1): 114-22.
[http://dx.doi.org/10.3171/2014.2.JNS131722] [PMID: 24702329]
[65]
Cotrim AP, Baum BJ. Gene therapy: Some history, applications, problems, and prospects. Toxicol Pathol 2008; 36(1): 97-103.
[http://dx.doi.org/10.1177/0192623307309925] [PMID: 18337227]
[66]
Iqubal A, Iqubal MK, Khan A, Ali J, Baboota S, Haque SE. Gene therapy, a novel therapeutic tool for neurological disorders: Current progress, challenges and future prospective. Curr Gene Ther 2020; 20(3): 184-94.
[http://dx.doi.org/10.2174/1566523220999200716111502] [PMID: 32674730]
[67]
Costantini LC, Bakowska JC, Breakefield XO, Isacson O. Gene therapy in the CNS. Gene Ther 2000; 7(2): 93-109.
[http://dx.doi.org/10.1038/sj.gt.3301119] [PMID: 10673714]
[68]
Wijekoon N, Gonawala L, Ratnayake P, et al. Gene therapy for selected neuromuscular and trinucleotide repeat disorders – An insight to subsume South Asia for multicenter clinical trials. IBRO Neuroscience Reports 2023; 14: 146-53.
[http://dx.doi.org/10.1016/j.ibneur.2023.01.009] [PMID: 36819775]
[69]
Slade N. Viral vectors in gene therapy. Period Biol 2001; 103(2): 139-44.
[70]
Simonato M, Bennett J, Boulis NM, et al. Progress in gene therapy for neurological disorders. Nat Rev Neurol 2013; 9(5): 277-91.
[http://dx.doi.org/10.1038/nrneurol.2013.56] [PMID: 23609618]
[71]
Boulaiz H, Marchal JA, Prados J, Melguizo C. Aránega A. Non-viral and viral vectors for gene therapy. Cell Mol Biol 2005; 51(1): 3-22.
[PMID: 16171561]
[72]
Arnedo A, Irache JM, Merodio M. Millán, MS. Albumin nanoparticles improved the stability, nuclear accumulation and anticytomegaloviral activity of a phosphodiester oligonucleotide. J Control Release 2004; 94(1): 217-27.
[http://dx.doi.org/10.1016/j.jconrel.2003.10.009] [PMID: 14684285]
[73]
Lv H, Zhang S, Wang B, Cui S, Yan J. Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release 2006; 114(1): 100-9.
[http://dx.doi.org/10.1016/j.jconrel.2006.04.014] [PMID: 16831482]
[74]
Ibraheem D, Elaissari A, Fessi H. Gene therapy and DNA delivery systems. Int J Pharm 2014; 459(1-2): 70-83.
[http://dx.doi.org/10.1016/j.ijpharm.2013.11.041] [PMID: 24286924]
[75]
Yamamoto A, Lucas JJ, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease. Cell 2000; 101(1): 57-66.
[http://dx.doi.org/10.1016/S0092-8674(00)80623-6] [PMID: 10778856]
[76]
Lee CYD, Cantle JP, Yang XW. Genetic manipulations of mutant huntingtin in mice: New insights into Huntington’s disease pathogenesis. FEBS J 2013; 280(18): 4382-94.
[http://dx.doi.org/10.1111/febs.12418] [PMID: 23829302]
[77]
Miniarikova J, Evers MM, Konstantinova P. Translation of microRNA-based huntingtin-lowering therapies from preclinical studies to the clinic. Mol Ther 2018; 26(4): 947-62.
[http://dx.doi.org/10.1016/j.ymthe.2018.02.002] [PMID: 29503201]
[78]
Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, et al. Targeting huntingtin expression in patients with Huntington’s disease. N Engl J Med 2019; 380(24): 2307-16.
[http://dx.doi.org/10.1056/NEJMoa1900907] [PMID: 31059641]
[79]
Rinaldi C, Wood MJA. Antisense oligonucleotides: The next frontier for treatment of neurological disorders. Nat Rev Neurol 2018; 14(1): 9-21.
[http://dx.doi.org/10.1038/nrneurol.2017.148] [PMID: 29192260]
[80]
Kordasiewicz HB, Stanek LM, Wancewicz EV, et al. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis. Neuron 2012; 74(6): 1031-44.
[http://dx.doi.org/10.1016/j.neuron.2012.05.009] [PMID: 22726834]
[81]
Carroll JB, Warby SC, Southwell AL, et al. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene/allele-specific silencing of mutant huntingtin. Mol Ther 2011; 19(12): 2178-85.
[http://dx.doi.org/10.1038/mt.2011.201] [PMID: 21971427]
[82]
Østergaard ME, Southwell AL, Kordasiewicz H, et al. Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS. Nucleic Acids Res 2013; 41(21): 9634-50.
[http://dx.doi.org/10.1093/nar/gkt725] [PMID: 23963702]
[83]
Bečanović K, Nørremølle A, Neal SJ, et al. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease. Nat Neurosci 2015; 18(6): 807-16.
[http://dx.doi.org/10.1038/nn.4014] [PMID: 25938884]
[84]
Aguiar S, van der Gaag B, Cortese FAB. RNAi mechanisms in Huntington’s disease therapy: siRNA versus shRNA. Transl Neurodegener 2017; 6(1): 30.
[http://dx.doi.org/10.1186/s40035-017-0101-9] [PMID: 29209494]
[85]
Rook ME, Southwell AL. Antisense oligonucleotide therapy: From design to the Huntington disease clinic. BioDrugs 2022; 36(2): 105-19.
[http://dx.doi.org/10.1007/s40259-022-00519-9] [PMID: 35254632]
[86]
Tabrizi SJ, Estevez-Fraga C, van Roon-Mom WMC, et al. Potential disease-modifying therapies for Huntington’s disease: Lessons learned and future opportunities. Lancet Neurol 2022; 21(7): 645-58.
[http://dx.doi.org/10.1016/S1474-4422(22)00121-1] [PMID: 35716694]
[87]
Byun S, Lee M, Kim M. Gene therapy for Huntington’s disease: The final strategy for a cure? J Mov Disord 2022; 15(1): 15-20.
[http://dx.doi.org/10.14802/jmd.21006] [PMID: 34781633]
[88]
Peplow PV, Martinez B. Altered microRNA expression in animal models of Huntington’s disease and potential therapeutic strategies. Neural Regen Res 2021; 16(11): 2159-69.
[http://dx.doi.org/10.4103/1673-5374.310673] [PMID: 33818488]
[89]
Rodrigues FB, Wild EJ. Huntington’s disease clinical trials corner: April 2020. J Huntingtons Dis 2020; 9(2): 185-97.
[http://dx.doi.org/10.3233/JHD-200002] [PMID: 32250312]
[90]
Shannon KM. Recent Advances in the treatment of Huntington’s Disease: Targeting DNA and RNA. CNS Drugs 2020; 34(3): 219-28.
[http://dx.doi.org/10.1007/s40263-019-00695-3] [PMID: 31933283]
[91]
Caron NS, Dorsey ER, Hayden MR. Therapeutic approaches to Huntington disease: From the bench to the clinic. Nat Rev Drug Discov 2018; 17(10): 729-50.
[http://dx.doi.org/10.1038/nrd.2018.133] [PMID: 30237454]
[92]
Zeitler B, Froelich S, Marlen K, et al. Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease. Nat Med 2019; 25(7): 1131-42.
[http://dx.doi.org/10.1038/s41591-019-0478-3] [PMID: 31263285]
[93]
Wild EJ, Tabrizi SJ. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol 2017; 16(10): 837-47.
[http://dx.doi.org/10.1016/S1474-4422(17)30280-6] [PMID: 28920889]
[94]
Jiang F, Doudna JA. CRISPR–Cas9 structures and mechanisms. Annu Rev Biophys 2017; 46(1): 505-29.
[http://dx.doi.org/10.1146/annurev-biophys-062215-010822] [PMID: 28375731]
[95]
Liang P, Xu Y, Zhang X, et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 2015; 6(5): 363-72.
[http://dx.doi.org/10.1007/s13238-015-0153-5] [PMID: 25894090]
[96]
Shin JW, Kim KH, Chao MJ, et al. Permanent inactivation of Huntington’s disease mutation by personalized allele-specific CRISPR/Cas9. Hum Mol Genet 2016; 25(20): ddw286.
[http://dx.doi.org/10.1093/hmg/ddw286] [PMID: 28172889]
[97]
Alkanli SS, Alkanli N, Ay A, Albeniz I. CRISPR/Cas9 mediated therapeutic approach in Huntington’s disease. Mol Neurobiol 2023; 60(3): 1486-98.
[http://dx.doi.org/10.1007/s12035-022-03150-5] [PMID: 36482283]
[98]
Alpaugh M, Galleguillos D, Forero J, et al. Disease‐modifying effects of ganglioside GM1 in Huntington’s disease models. EMBO Mol Med 2017; 9(11): 1537-57.
[http://dx.doi.org/10.15252/emmm.201707763] [PMID: 28993428]
[99]
Maglione V, Marchi P, Di Pardo A, et al. Impaired ganglioside metabolism in Huntington’s disease and neuroprotective role of GM1. J Neurosci 2010; 30(11): 4072-80.
[http://dx.doi.org/10.1523/JNEUROSCI.6348-09.2010] [PMID: 20237277]
[100]
Di Pardo A, Maglione V, Alpaugh M, et al. Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice. Proc Natl Acad Sci USA 2012; 109(9): 3528-33.
[http://dx.doi.org/10.1073/pnas.1114502109] [PMID: 22331905]
[101]
Sadri-Vakili G, Cha JHJ. Mechanisms of Disease: Histone modifications in Huntington’s disease. Nat Clin Pract Neurol 2006; 2(6): 330-8.
[http://dx.doi.org/10.1038/ncpneuro0199] [PMID: 16932577]
[102]
Süssmuth SD, Haider S, Landwehrmeyer GB, et al. An exploratory double‐blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntington’s disease. Br J Clin Pharmacol 2015; 79(3): 465-76.
[http://dx.doi.org/10.1111/bcp.12512] [PMID: 25223731]
[103]
Cardinale A, Fusco FR. Inhibition of phosphodiesterases as a strategy to achieve neuroprotection in Huntington’s disease. CNS Neurosci Ther 2018; 24(4): 319-28.
[http://dx.doi.org/10.1111/cns.12834] [PMID: 29500937]
[104]
Hebb ALO, Robertson HA, Denovan-Wright EM. Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington′s disease transgenic mice prior to the onset of motor symptoms. Neuroscience 2004; 123(4): 967-81.
[http://dx.doi.org/10.1016/j.neuroscience.2003.11.009] [PMID: 14751289]
[105]
Giralt A, Saavedra A. Carretón O, et al. PDE10 inhibition increases GluA1 and CREB phosphorylation and improves spatial and recognition memories in a Huntington’s disease mouse model. Hippocampus 2013; 23(8): 684-95.
[http://dx.doi.org/10.1002/hipo.22128] [PMID: 23576401]
[106]
Ginés S, Bosch M, Marco S, et al. Reduced expression of the TrkB receptor in Huntington’s disease mouse models and in human brain. Eur J Neurosci 2006; 23(3): 649-58.
[http://dx.doi.org/10.1111/j.1460-9568.2006.04590.x] [PMID: 16487146]
[107]
Todd D, Gowers I, Dowler SJ, et al. A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington’s disease. PLoS One 2014; 9(2): e87923.
[http://dx.doi.org/10.1371/journal.pone.0087923] [PMID: 24503862]
[108]
Thevandavakkam MA, Schwarcz R, Muchowski PJ, Giorgini F. Targeting kynurenine 3-monooxygenase (KMO): Implications for therapy in Huntington’s disease. CNS Neurol Disord Drug Targets 2010; 9(6): 791-800.
[http://dx.doi.org/10.2174/187152710793237430] [PMID: 20942784]
[109]
Campesan S, Green EW, Breda C, et al. The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington’s disease. Curr Biol 2011; 21(11): 961-6.
[http://dx.doi.org/10.1016/j.cub.2011.04.028] [PMID: 21636279]
[110]
Jia H, Wang Y, Morris CD, et al. The effects of pharmacological inhibition of Histone Deacetylase 3 (HDAC3) in Huntington’s Disease mice. PLoS One 2016; 11(3): e0152498.
[http://dx.doi.org/10.1371/journal.pone.0152498] [PMID: 27031333]
[111]
Ferrante RJ, Kubilus JK, Lee J, et al. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington’s disease mice. J Neurosci 2003; 23(28): 9418-27.
[http://dx.doi.org/10.1523/JNEUROSCI.23-28-09418.2003] [PMID: 14561870]
[112]
Ravikumar B, Imarisio S, Sarkar S, O’Kane CJ, Rubinsztein DC. Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. J Cell Sci 2008; 121(10): 1649-60.
[http://dx.doi.org/10.1242/jcs.025726] [PMID: 18430781]
[113]
Fox LM, Kim K, Johnson CW, et al. Huntington’s Disease pathogenesis is modified in vivo by Alfy/Wdfy3 and selective macroautophagy. Neuron 2020; 105(5): 813-821.e6.
[http://dx.doi.org/10.1016/j.neuron.2019.12.003] [PMID: 31899071]
[114]
Monk R, Connor B. Cell replacement therapy for Huntington’s Disease. Adv Exp Med Biol 2020; 1266: 57-69.
[http://dx.doi.org/10.1007/978-981-15-4370-8_5] [PMID: 33105495]
[115]
Tartaglione AM, Popoli P, Calamandrei G. Regenerative medicine in Huntington’s disease: Strengths and weaknesses of preclinical studies. Neurosci Biobehav Rev 2017; 77: 32-47.
[http://dx.doi.org/10.1016/j.neubiorev.2017.02.017] [PMID: 28223129]
[116]
Carri AD, Onorati M, Lelos MJ, et al. Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons. Development 2013; 140(2): 301-12.
[http://dx.doi.org/10.1242/dev.084608] [PMID: 23250204]
[117]
Arber C, Precious SV, Cambray S, et al. Activin A directs striatal projection neuron differentiation of human pluripotent stem cells. Development 2015; 142(7): 1375-86.
[http://dx.doi.org/10.1242/dev.117093] [PMID: 25804741]
[118]
Faedo A, Laporta A, Segnali A, et al. Differentiation of human telencephalic progenitor cells into MSNs by inducible expression of Gsx2 and Ebf1. Proc Natl Acad Sci USA 2017; 114(7): E1234-42.
[http://dx.doi.org/10.1073/pnas.1611473114] [PMID: 28137879]
[119]
Kendall AL, Rayment FD, Torres EM, Baker HF, Ridley RM, Dunnett SB. Functional integration of striatal allografts in a primate model of Huntington’s disease. Nat Med 1998; 4(6): 727-9.
[http://dx.doi.org/10.1038/nm0698-727] [PMID: 9623985]
[120]
Dunnett SB, Nathwani F. Björklund A. The integration and function of striatal grafts. Prog Brain Res 2000; 127: 345-80.
[http://dx.doi.org/10.1016/S0079-6123(00)27017-9] [PMID: 11142035]
[121]
Deckel AW, Moran TH, Coyle JT, Sanberg PR, Robinson RG. Anatomical predictors of behavioral recovery following fetal striatal transplants. Brain Res 1986; 365(2): 249-58.
[http://dx.doi.org/10.1016/0006-8993(86)91636-7] [PMID: 3947993]
[122]
Isacson O, Dunnett SB, Björklund A. Graft-induced behavioral recovery in an animal model of Huntington disease. Proc Natl Acad Sci USA 1986; 83(8): 2728-32.
[http://dx.doi.org/10.1073/pnas.83.8.2728] [PMID: 2939457]
[123]
Pritzel M, Isacson O, Brundin P, Wiklund L, Björklund A. Afferent and efferent connections of striatal grafts implanted into the ibotenic acid lesioned neostriatum in adult rats. Exp Brain Res 1986; 65(1): 112-26.
[http://dx.doi.org/10.1007/BF00243834] [PMID: 2433142]
[124]
Sirinathsinghji DJS, Dunnett SB, Isacson O, Clarke DJ, Kendrick K, Björklund A. Striatal grafts in rats with unilateral neostriatal lesions—II. In vivo monitoring of gaba release in globus pallidus and substantia nigra. Neuroscience 1988; 24(3): 803-11.
[http://dx.doi.org/10.1016/0306-4522(88)90068-1] [PMID: 3380300]
[125]
Clarke DJ, Dunnett SB, Isacson O. Björklund A. Striatal grafts in the ibotenic acid-lesioned neostriatum: Ultrastructural and immunocytochemical studies. Prog Brain Res 1988; 78: 47-53.
[http://dx.doi.org/10.1016/S0079-6123(08)60265-4] [PMID: 3247443]
[126]
Clarke DJ, Dunnett SB, Isacson O, Sirinathsinghji DJS, Björklund A. Striatal grafts in rats with unilateral neostriatal lesions—I. Ultrastructural evidence of afferent synaptic inputs from the host nigrostriatal pathway. Neuroscience 1988; 24(3): 791-801.
[http://dx.doi.org/10.1016/0306-4522(88)90067-X] [PMID: 2898109]
[127]
Dunnett SB, Isacson O, Sirinathsinghji DJS, Clarke DJ, Björklund A. Striatal grafts in rats with unilateral neostriatal lesions—III. Recovery from dopamine-dependent motor asymmetry and deficits in skilled paw reaching. Neuroscience 1988; 24(3): 813-20.
[http://dx.doi.org/10.1016/0306-4522(88)90069-3] [PMID: 3380301]
[128]
Dunnett SB, Isacson O, Sirinathsinghji DJS, Clarke DJ. Björklund A. Striatal grafts in the ibotenic acid-lesioned neostriatum: Functional studies. Prog Brain Res. 1988; 78: pp. 39-45.
[http://dx.doi.org/10.1016/S0079-6123(08)60264-2] [PMID: 3073422]
[129]
Palfi S, Condé F, Riche D, et al. Fetal striatal allografts reverse cognitive deficits in a primate model of Huntington disease. Nat Med 1998; 4(8): 963-6.
[http://dx.doi.org/10.1038/nm0898-963] [PMID: 9701252]
[130]
Nakao N, Itakura T. Fetal tissue transplants in animal models of Huntington’s disease: The effects on damaged neuronal circuitry and behavioral deficits. Prog Neurobiol 2000; 61(3): 313-38.
[http://dx.doi.org/10.1016/S0301-0082(99)00058-1] [PMID: 10727778]
[131]
Freeman TB, Hauser RA, Willing AE, Zigova T, Sanberg PR, Saporta S. Transplantation of human fetal striatal tissue in Huntington’s disease: Rationale for clinical studies. Novartis Found Symp 2000; 231: 129-38.
[http://dx.doi.org/10.1002/0470870834.ch8] [PMID: 11131535]
[132]
Klein A, Lane EL, Dunnett SB. Brain repair in a unilateral rat model of Huntington’s disease: New insights into impairment and restoration of forelimb movement patterns. Cell Transplant 2013; 22(10): 1735-51.
[http://dx.doi.org/10.3727/096368912X657918] [PMID: 23067670]
[133]
Cisbani G, Saint-Pierre M, Cicchetti F. Single-cell suspension methodology favors survival and vascularization of fetal striatal grafts in the YAC128 mouse model of Huntington’s disease. Cell Transplant 2014; 23(10): 1267-78.
[http://dx.doi.org/10.3727/096368913X668636] [PMID: 23768945]
[134]
Bachoud-Lévi AC. Human fetal cell therapy in Huntington’s Disease: A randomized, multicenter, phase II trial. Mov Disord 2020; 35(8): 1323-35.
[http://dx.doi.org/10.1002/mds.28201] [PMID: 32666599]
[135]
Arnhold S, Lenartz D, Kruttwig K, et al. Differentiation of green fluorescent protein-labeled embryonic stem cell-derived neural precursor cells into Thy-1-positive neurons and glia after transplantation into adult rat striatum. J Neurosurg 2000; 93(6): 1026-32.
[http://dx.doi.org/10.3171/jns.2000.93.6.1026] [PMID: 11117845]
[136]
Nasonkin I, Mahairaki V, Xu L, et al. Long-term, stable differentiation of human embryonic stem cell-derived neural precursors grafted into the adult mammalian neostriatum. Stem Cells 2009; 27(10): 2414-26.
[http://dx.doi.org/10.1002/stem.177] [PMID: 19609935]
[137]
Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 2000; 24(4): 372-6.
[http://dx.doi.org/10.1038/74199] [PMID: 10742100]
[138]
Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 2003; 113(5): 643-55.
[http://dx.doi.org/10.1016/S0092-8674(03)00392-1] [PMID: 12787505]
[139]
Chew JL, Loh YH, Zhang W, et al. Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol 2005; 25(14): 6031-46.
[http://dx.doi.org/10.1128/MCB.25.14.6031-6046.2005] [PMID: 15988017]
[140]
Michelsen KA, Acosta-Verdugo S, Benoit-Marand M, et al. Area-specific reestablishment of damaged circuits in the adult cerebral cortex by cortical neurons derived from mouse embryonic stem cells. Neuron 2015; 85(5): 982-97.
[http://dx.doi.org/10.1016/j.neuron.2015.02.001] [PMID: 25741724]
[141]
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663-76.
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[142]
Park IH, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells. Cell 2008; 134(5): 877-86.
[http://dx.doi.org/10.1016/j.cell.2008.07.041] [PMID: 18691744]
[143]
Zhang N, An MC, Montoro D, Ellerby LM. Characterization of human Huntington’s disease cell model from induced pluripotent stem cells. PLoS Curr 2010; 2: RRN1193.
[http://dx.doi.org/10.1371/currents.RRN1193] [PMID: 21037797]
[144]
Chae JI, Kim DW, Lee N, et al. Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington’s disease patient. Biochem J 2012; 446(3): 359-71.
[http://dx.doi.org/10.1042/BJ20111495] [PMID: 22694310]
[145]
Jeon I, Lee N, Li JY, et al. Neuronal properties, in vivo effects, and pathology of a Huntington’s disease patient-derived induced pluripotent stem cells. Stem Cells 2012; 30(9): 2054-62.
[http://dx.doi.org/10.1002/stem.1135] [PMID: 22628015]
[146]
Jeon I, Choi C, Lee N, et al. In vivo roles of a patient-derived induced pluripotent stem cell line (HD72-iPSC) in the YAC128 model of Huntington’s disease. Int J Stem Cells 2014; 7(1): 43-7.
[http://dx.doi.org/10.15283/ijsc.2014.7.1.43] [PMID: 24921027]
[147]
An MC, Zhang N, Scott G, et al. Genetic correction of Huntington’s disease phenotypes in induced pluripotent stem cells. Cell Stem Cell 2012; 11(2): 253-63.
[http://dx.doi.org/10.1016/j.stem.2012.04.026] [PMID: 22748967]
[148]
Kerkis I, Haddad MS, Valverde CW, Glosman S. Neural and mesenchymal stem cells in animal models of Huntington’s disease: Past experiences and future challenges. Stem Cell Res Ther 2015; 6(1): 232.
[http://dx.doi.org/10.1186/s13287-015-0248-1] [PMID: 26667114]
[149]
Bantubungi K, Blum D, Cuvelier L, et al. Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington’s disease. Mol Cell Neurosci 2008; 37(3): 454-70.
[http://dx.doi.org/10.1016/j.mcn.2007.11.001] [PMID: 18083596]
[150]
Snyder BR, Chiu AM, Prockop DJ, Chan AWS. Human multipotent stromal cells (MSCs) increase neurogenesis and decrease atrophy of the striatum in a transgenic mouse model for Huntington’s disease. PLoS One 2010; 5(2): e9347.
[http://dx.doi.org/10.1371/journal.pone.0009347] [PMID: 20179764]
[151]
Fink KD, Rossignol J, Crane AT, et al. Transplantation of umbilical cord-derived mesenchymal stem cells into the striata of R6/2 mice: Behavioral and neuropathological analysis. Stem Cell Res Ther 2013; 4(5): 130.
[http://dx.doi.org/10.1186/scrt341] [PMID: 24456799]
[152]
Lee ST, Chu K, Jung KH, et al. Slowed progression in models of huntington disease by adipose stem cell transplantation. Ann Neurol 2009; 66(5): 671-81.
[http://dx.doi.org/10.1002/ana.21788] [PMID: 19938161]
[153]
Lin YT, Chern Y, Shen CKJ, et al. Human mesenchymal stem cells prolong survival and ameliorate motor deficit through trophic support in Huntington’s disease mouse models. PLoS One 2011; 6(8): e22924.
[http://dx.doi.org/10.1371/journal.pone.0022924] [PMID: 21850243]
[154]
Moraes L, Vasconcelos-dos-Santos A, Santana FC, et al. Neuroprotective effects and magnetic resonance imaging of mesenchymal stem cells labeled with SPION in a rat model of Huntington’s disease. Stem Cell Res (Amst) 2012; 9(2): 143-55.
[http://dx.doi.org/10.1016/j.scr.2012.05.005] [PMID: 22742973]
[155]
Jiang Y, Lv H, Huang S, Tan H, Zhang Y, Li H. Bone marrow mesenchymal stem cells can improve the motor function of a Huntington’s disease rat model. Neurol Res 2011; 33(3): 331-7.
[http://dx.doi.org/10.1179/016164110X12816242542571] [PMID: 21513650]
[156]
Rossignol J, Boyer C, Lévèque X, et al. Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington’s disease: Morphological and behavioral outcomes. Behav Brain Res 2011; 217(2): 369-78.
[http://dx.doi.org/10.1016/j.bbr.2010.11.006] [PMID: 21070819]
[157]
Mullen RJ, Buck CR, Smith AM. NeuN, a neuronal specific nuclear protein in vertebratesxs. Development 1992; 116(1): 201-11.
[http://dx.doi.org/10.1242/dev.116.1.201] [PMID: 1483388]
[158]
Liang XS, Sun ZW, Thomas AM, Li S. Mesenchymal stem cell therapy for Huntington Disease: A meta-analysis. Stem Cells Int 2023; 2023116: 1109967.
[http://dx.doi.org/10.1155/2023/1109967]
[159]
Rossignol J, Fink K, Davis K, et al. Transplants of adult mesenchymal and neural stem cells provide neuroprotection and behavioral sparing in a transgenic rat model of Huntington’s disease. Stem Cells 2014; 32(2): 500-9.
[http://dx.doi.org/10.1002/stem.1508] [PMID: 23939879]
[160]
Choi KA, Hong S. Induced neural stem cells as a means of treatment in Huntington’s disease. Expert Opin Biol Ther 2017; 17(11): 1-11.
[http://dx.doi.org/10.1080/14712598.2017.1365133] [PMID: 28792249]
[161]
Nakao N, Ogura M, Nakai K, Itakura T. Embryonic striatal grafts restore neuronal activity of the globus pallidus in a rodent model of Huntington’s disease. Neuroscience 1999; 88(2): 469-77.
[http://dx.doi.org/10.1016/S0306-4522(98)00197-3] [PMID: 10197767]
[162]
Yang CR, Yu RK. Intracerebral transplantation of neural stem cells combined with trehalose ingestion alleviates pathology in a mouse model of Huntington’s disease. J Neurosci Res 2009; 87(1): 26-33.
[http://dx.doi.org/10.1002/jnr.21817] [PMID: 18683244]
[163]
Aubry L, Bugi A, Lefort N, Rousseau F, Peschanski M, Perrier AL. Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proc Natl Acad Sci USA 2008; 105(43): 16707-12.
[http://dx.doi.org/10.1073/pnas.0808488105] [PMID: 18922775]
[164]
McBride JL, Behrstock SP, Chen EY, et al. Human neural stem cell transplants improve motor function in a rat model of Huntington’s disease. J Comp Neurol 2004; 475(2): 211-9.
[http://dx.doi.org/10.1002/cne.20176] [PMID: 15211462]
[165]
Johann V, Schiefer J, Sass C, et al. Time of transplantation and cell preparation determine neural stem cell survival in a mouse model of Huntington’s disease. Exp Brain Res 2007; 177(4): 458-70.
[http://dx.doi.org/10.1007/s00221-006-0689-y] [PMID: 17013619]
[166]
Ryu JK, Kim J, Cho SJ, et al. Proactive transplantation of human neural stem cells prevents degeneration of striatal neurons in a rat model of Huntington disease. Neurobiol Dis 2004; 16(1): 68-77.
[http://dx.doi.org/10.1016/j.nbd.2004.01.016] [PMID: 15207263]
[167]
ClinicalTrials.gov. Available From www.clinicaltrials.gov
[168]
Rosser AE, Busse ME, Gray WP, et al. Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder. Brain 2022; 145(5): 1584-97.
[http://dx.doi.org/10.1093/brain/awac086] [PMID: 35262656]
[169]
Puhl DL, D’Amato AR, Gilbert RJ. Challenges of gene delivery to the central nervous system and the growing use of biomaterial vectors. Brain Res Bull 2019; 150: 216-30.
[http://dx.doi.org/10.1016/j.brainresbull.2019.05.024] [PMID: 31173859]
[170]
Piguet F, de Saint Denis T, Audouard E, et al. The challenge of gene therapy for neurological diseases: Strategies and tools to achieve efficient delivery to the central nervous system. Hum Gene Ther 2021; 32(7-8): 349-74.
[http://dx.doi.org/10.1089/hum.2020.105] [PMID: 33167739]
[171]
Lelos MJ. Investigating cell therapies in animal models of Parkinson’s and Huntington’s disease: Current challenges and considerations International Review of Neurobiology. Amsterdam: Elsevier 2022; pp. 159-89.
[172]
Shen F, Fan Y, Su H, et al. Adeno-associated viral vector-mediated hypoxia-regulated VEGF gene transfer promotes angiogenesis following focal cerebral ischemia in mice. Gene Ther 2008; 15(1): 30-9.
[http://dx.doi.org/10.1038/sj.gt.3303048] [PMID: 17960159]
[173]
Smith KR. Gene therapy: The potential applicability of gene transfer technology to the human germline. Int J Med Sci 2004; 1(2): 76-91.
[http://dx.doi.org/10.7150/ijms.1.76] [PMID: 15912200]
[174]
Gore ME. Adverse effects of gene therapy: Gene therapy can cause leukaemia: No shock, mild horror but a probe. Gene Ther 2003; 10(1): 4.
[http://dx.doi.org/10.1038/sj.gt.3301946]
[175]
Thrasher AJ, Williams DA. Evolving gene therapy in primary immunodeficiency. Mol Ther 2017; 25(5): 1132-41.
[http://dx.doi.org/10.1016/j.ymthe.2017.03.018] [PMID: 28366768]
[176]
Pena SA, Iyengar R, Eshraghi RS, et al. Gene therapy for neurological disorders: Challenges and recent advancements. J Drug Target 2020; 28(2): 111-28.
[http://dx.doi.org/10.1080/1061186X.2019.1630415] [PMID: 31195838]
[177]
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]
[178]
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJA. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011; 29(4): 341-5.
[http://dx.doi.org/10.1038/nbt.1807] [PMID: 21423189]
[179]
Fan CH, Ting CY, Lin CY, et al. Noninvasive, Targeted and Non-Viral Ultrasound-Mediated GDNF-Plasmid Delivery for Treatment of Parkinson’s Disease. Sci Rep 2016; 6(1): 19579.
[http://dx.doi.org/10.1038/srep19579] [PMID: 26786201]
[180]
Li Y, Wang J, Lee CGL, et al. CNS gene transfer mediated by a novel controlled release system based on DNA complexes of degradable polycation PPE-EA: A comparison with polyethylenimine/DNA complexes. Gene Ther 2004; 11(1): 109-14.
[http://dx.doi.org/10.1038/sj.gt.3302135] [PMID: 14681704]
[181]
Joshi CR, Labhasetwar V, Ghorpade A. Destination brain: The past, present, and future of therapeutic gene delivery. J Neuroimmune Pharmacol 2017; 12(1): 51-83.
[http://dx.doi.org/10.1007/s11481-016-9724-3] [PMID: 28160121]
[182]
van Tellingen O, Yetkin-Arik B, de Gooijer MC, Wesseling P, Wurdinger T, de Vries HE. Overcoming the blood–brain tumor barrier for effective glioblastoma treatment. Drug Resist Updat 2015; 19: 1-12.
[http://dx.doi.org/10.1016/j.drup.2015.02.002] [PMID: 25791797]
[183]
Koltover I, Salditt T, Rädler JO, Safinya CR. An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science 1998; 281(5373): 78-81.
[http://dx.doi.org/10.1126/science.281.5373.78] [PMID: 9651248]
[184]
Kumar P, Wu H, McBride JL, et al. Transvascular delivery of small interfering RNA to the central nervous system. Nature 2007; 448(7149): 39-43.
[http://dx.doi.org/10.1038/nature05901] [PMID: 17572664]
[185]
Foged C, Nielsen HM. Cell-penetrating peptides for drug delivery across membrane barriers. Expert Opin Drug Deliv 2008; 5(1): 105-17.
[http://dx.doi.org/10.1517/17425247.5.1.105] [PMID: 18095931]
[186]
Salado-Manzano C. Perpiña U, Straccia M, et al. Is the immunological response a bottleneck for cell therapy in neurodegenerative diseases? Front Cell Neurosci 2020; 14: 250.
[http://dx.doi.org/10.3389/fncel.2020.00250] [PMID: 32848630]
[187]
Drew CJG, Busse M. Considerations for clinical trial design and conduct in the evaluation of novel advanced therapeutics in neurodegenerative disease International Review of Neurobiology. Amsterdam: Elsevier 2022; pp. 235-79.
[188]
European Medicines Agency. Guideline on human cell-based medicinal products. 2008. Available From https://www.ema. europa.eu/en/documents/scientific-guideline/guideline-human-cell-based-medicinal-products_en.pdf
[189]
Food and Drug Administration. Human cells, tissues, and cellular and tissue-based products. 2015. Available From https://www.federalregister.gov/documents/2001/01/19/01-1126/human-cells-tissues-and-cellular-and-tissue-based-products-establishment-registration-and-listing
[190]
Food and Drug Administration, Guidance for FDA reviewers and sponsors. 2003. Available From https://www.fda.gov/media/73624/download
[191]
Food and Drug Administration. Proposed approach to regulation of cellular and tissue-based products. 1997. Available From https://www.fda.gov/regulatory-information/search-fda-guidance-documents/proposed-approach-regulation-cellular-and-tissue-based-products
[192]
European Medicines Agency. Reflection paper on stem cell-based medicinal products. 2010. Available From https://www.ema. europa.eu/en/documents/scientific-guideline/draft-reflection-paper-stem-cell-based-medicinal-products_en.pdf
[193]
International Society for Stem Cell Research. Guidelines for the clinical translation of stem cells. 2008. Available From https://www.isscr.org/guidelines
[194]
Food and Drug Administration. CTGTAC Meeting # 45. Cellular therapies derived from human embryonic stem cells – Considerations for pre-clinical safety testing and patient monitoring. 2008.
[195]
Klug B, Reinhardt J, Schröder C. Requirements for long-term follow-up on efficacy and safety of advanced therapy medicinal products. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2010; 53(1): 58-62.
[http://dx.doi.org/10.1007/s00103-009-0992-4] [PMID: 19949763]
[196]
Harper SQ, Staber PD, He X, et al. RNA interference improves motor and neuropathological abnormalities in a Huntington’s disease mouse model. Proc Natl Acad Sci USA 2005; 102(16): 5820-5.
[http://dx.doi.org/10.1073/pnas.0501507102] [PMID: 15811941]
[197]
Ekman FK, Ojala DS, Adil MM, Lopez PA, Schaffer DV, Gaj T. CRISPR-Cas9-mediated genome editing increases lifespan and improves motor deficits in a Huntington’s disease mouse model. Mol Ther Nucleic Acids 2019; 17: 829-39.
[http://dx.doi.org/10.1016/j.omtn.2019.07.009] [PMID: 31465962]
[198]
Chen W, Hu Y, Ju D. Gene therapy for neurodegenerative disorders: Aadvances, insights and prospects. Acta Pharm Sin B 2020; 10(8): 1347-59.
[http://dx.doi.org/10.1016/j.apsb.2020.01.015] [PMID: 32963936]
[199]
Tabrizi SJ, Ghosh R, Leavitt BR. Huntingtin lowering strategies for disease modification in Huntington’s disease. Neuron 2019; 101(5): 801-19.
[http://dx.doi.org/10.1016/j.neuron.2019.01.039] [PMID: 30844400]
[200]
Beatriz M, Lopes C, Ribeiro ACS, Rego ACC. Revisiting cell and gene therapies in Huntington’s disease. J Neurosci Res 2021; 99(7): 1744-62.
[http://dx.doi.org/10.1002/jnr.24845] [PMID: 33881180]
[201]
Kerkis I, Araldi RP, Wenceslau CV, Mendes TB. Advances in cellular and cell-free therapy medicinal products for Huntington disease treatmentFrom Pathophysiology to Treatment of Huntington’s Disease. London: IntechOpen 2022.
[http://dx.doi.org/10.5772/intechopen.102539]
[202]
Conner LT, Srinageshwar B, Bakke JL, Dunbar GL, Rossignol J. Advances in stem cell and other therapies for Huntington’s disease: An update. Brain Res Bull 2023; 199: 110673.
[http://dx.doi.org/10.1016/j.brainresbull.2023.110673] [PMID: 37257627]
[203]
Duan W, Urani E, Mattson MP. The potential of gene editing for Huntington’s disease. Trends Neurosci 2023; 46(5): 365-76.
[http://dx.doi.org/10.1016/j.tins.2023.02.005] [PMID: 36907678]
[204]
Bachoud-Lévi AC, Massart R, Rosser A. Cell therapy in Huntington’s disease: Taking stock of past studies to move the field forward. Stem Cells 2021; 39(2): 144-55.
[http://dx.doi.org/10.1002/stem.3300] [PMID: 33176057]

Rights & Permissions Print Cite
Article Metrics
12
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy