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Volume 20, Issue 1
  • ISSN: 2772-4328
  • E-ISSN: 2772-4336

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.

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2025-01-08

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References

  1. WexlerA. WildE.J. TabriziS.J. George Huntington: A legacy of inquiry, empathy and hope.Brain201613982326233310.1093/brain/aww165 27421790
     [Google Scholar]
  2. RawlinsM.D. WexlerN.S. WexlerA.R. The prevalence of Huntington’s Disease.Neuroepidemiology201646214415310.1159/000443738 26824438
     [Google Scholar]
  3. BarkerR.A. FujimakiM. RogersP. RubinszteinD.C. Huntingtin-lowering strategies for Huntington’s disease.Expert Opin. Investig. Drugs202029101125113210.1080/13543784.2020.1804552 32745442
     [Google Scholar]
  4. van DuijnE. FernandesA.R. AbreuD. WareJ.J. NeacyE. SampaioC. Incidence of completed suicide and suicide attempts in a global prospective study of Huntington’s disease.BJPsych Open202175e15810.1192/bjo.2021.969
     [Google Scholar]
  5. European Medicines Agency. Advanced therapy medicinal products.2017Available From: https://www.ema.europa.eu/en/human-regulatory-overview/advanced-therapy-medicinal-productsoverview
    [Google Scholar]
  6. GalliM.C. ATMPs for Cancer immunotherapy: A regulatory overview.Methods Mol. Biol.201613931910.1007/978‑1‑4939‑3338‑9_1 27033211
     [Google Scholar]
  7. Hossein-KhannazerN. VosoughM. SalahiS. MousaviM.A. AziziG. Stem cell-based and advanced therapeutic modalities for Parkinson’s disease: A risk-effectiveness patient-centered analysis.Curr. Neuropharmacol.202220122320234510.2174/1570159X20666220201100238 35105291
     [Google Scholar]
  8. MeijP. CanalsJ.M. LoweryM. ScottM. Advanced therapy medicinal products.Leuven, BelgiumLERU2019
     [Google Scholar]
  9. KayC. HaydenM.R. LeavittB.R. Epidemiology of huntington disease.Handb. Clin. Neurol.2017144314610.1016/B978‑0‑12‑801893‑4.00003‑1 28947124
     [Google Scholar]
  10. ParadisiI. Hernández A, Arias S. Huntington disease mutation in Venezuela: Age of onset, haplotype analyses and geographic aggregation.J. Hum. Genet.200853212713510.1007/s10038‑007‑0227‑1 18157708
     [Google Scholar]
  11. MedinaA. MahjoubY. ShaverL. PringsheimT. Prevalence and incidence of Huntington’s disease: An updated systematic review and meta‐analysis.Mov. Disord.202237122327233510.1002/mds.29228 36161673
     [Google Scholar]
  12. BaigS.S. StrongM. QuarrellO.W.J. The global prevalence of Huntington’s disease: A systematic review and discussion.Neurodegener. Dis. Manag.20166433134310.2217/nmt‑2016‑0008 27507223
     [Google Scholar]
  13. WalkerF.O. Huntington’s disease.Lancet2007369955721822810.1016/S0140‑6736(07)60111‑1 17240289
     [Google Scholar]
  14. YoungA.B. Huntingtin in health and disease.J. Clin. Invest.2003111329930210.1172/JCI17742 12569151
     [Google Scholar]
  15. WankerE.E. AstA. SchindlerF. TrepteP. SchnoeglS. The pathobiology of perturbed mutant huntingtin protein–protein interactions in Huntington’s disease.J. Neurochem.2019151450751910.1111/jnc.14853 31418858
     [Google Scholar]
  16. TabriziS.J. FlowerM.D. RossC.A. WildE.J. Huntington disease: New insights into molecular pathogenesis and therapeutic opportunities.Nat. Rev. Neurol.2020161052954610.1038/s41582‑020‑0389‑4 32796930
     [Google Scholar]
  17. DongX. ZongS. WittingA. LindenbergK.S. KochanekS. HuangB. Adenovirus vector‐based in vitro neuronal cell model for Huntington’s disease with human disease‐like differential aggregation and degeneration.J. Gene Med.201214746848110.1002/jgm.2641 22700462
     [Google Scholar]
  18. PandeyM. RajammaU. Huntington’s disease: The coming of age.J. Genet.201897364966410.1007/s12041‑018‑0957‑1 30027901
     [Google Scholar]
  19. LipeH. BirdT. Late onset Huntington Disease: Clinical and genetic characteristics of 34 cases.J. Neurol. Sci.20092761-2159162
     [Google Scholar]
  20. FrankS. Treatment of Huntington’s disease.Neurotherapeutics201411115316010.1007/s13311‑013‑0244‑z 24366610
     [Google Scholar]
  21. DickeyA.S. La SpadaA.R. Therapy development in Huntington disease: From current strategies to emerging opportunities.Am. J. Med. Genet. A.2018176484286110.1002/ajmg.a.38494 29218782
     [Google Scholar]
  22. KumarA. KumarV. SinghK. Therapeutic advances for Huntington’s disease.Brain Sci.20201014310.3390/brainsci10010043 31940909
     [Google Scholar]
  23. StahlC.M. FeiginA. Medical, surgical, and genetic treatment of Huntington disease.Neurol. Clin.202038236737810.1016/j.ncl.2020.01.010 32279715
     [Google Scholar]
  24. KimA. LalondeK. TruesdellA. New avenues for the treatment of Huntington’s disease.Int. J. Mol. Sci.20212216836310.3390/ijms22168363 34445070
     [Google Scholar]
  25. MestreT. FerreiraJ. CoelhoM.M. RosaM. SampaioC. Therapeutic interventions for disease progression in Huntington’s disease.Cochrane Database Syst. Rev.200920093CD00645510.1002/14651858.CD006455.pub2
     [Google Scholar]
  26. VenutoC.S. McGarryA. MaQ. KieburtzK. Pharmacologic approaches to the treatment of Huntington’s disease.Mov. Disord.2012271314110.1002/mds.23953 21997232
     [Google Scholar]
  27. JankovicJ. Clarence-SmithK. Tetrabenazine for the treatment of chorea and other hyperkinetic movement disorders.Expert Rev. Neurother.201111111509152310.1586/ern.11.149 22014129
     [Google Scholar]
  28. WyantK.J. RidderA.J. DayaluP. Huntington’s disease—update on treatments.Curr. Neurol. Neurosci. Rep.20171743310.1007/s11910‑017‑0739‑9 28324302
     [Google Scholar]
  29. FrankS. Effect of Deutetrabenazine on chorea among patients with huntington disease a randomized clinical trial.JAMA201631614050
     [Google Scholar]
  30. ClaassenD.O. CarrollB. De BoerL.M. Indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease.J. Clin. Mov. Disord.201741310.1186/s40734‑017‑0051‑5 28265459
     [Google Scholar]
  31. LoyC. ClaassenD.O. ColcherA. DavisC.S. DukerA. EberlyS.W. Safety of converting from tetrabenazine to deutetrabenazine for the treatment of Chorea.JAMA Neurol.2017748977982
     [Google Scholar]
  32. Furr StimmingE. ClaassenD.O. KaysonE. 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.202322649450410.1016/S1474‑4422(23)00127‑8 37210099
     [Google Scholar]
  33. BurgunderJ.M. GuttmanM. PerlmanS. GoodmanN. van KammenD.P. GoodmanL. An international survey-based algorithm for the pharmacologic treatment of chorea in Huntington’s disease.PLoS Curr.20113RRN126010.1371/currents.RRN1260 21975581
     [Google Scholar]
  34. ArmstrongM.J. Evidence-based guideline: Pharmacologic treatment of chorea in Huntington disease.Neurology20127936597603
     [Google Scholar]
  35. CoppenE.M. RoosR.A.C. Current pharmacological approaches to reduce chorea in Huntington’s disease.Drugs2017771294610.1007/s40265‑016‑0670‑4 27988871
     [Google Scholar]
  36. DallocchioC. BuffaC. TinelliC. MazzarelloP. Effectiveness of risperidone in Huntington chorea patients.J. Clin. Psychopharmacol.199919110110310.1097/00004714‑199902000‑00020 9934953
     [Google Scholar]
  37. PrillerJ. EckerD. LandwehrmeyerB. CraufurdD. A Europe‐wide assessment of current medication choices in Huntington’s disease.Mov. Disord.20082312178810.1002/mds.22188 18649399
     [Google Scholar]
  38. LucettiC. GambacciniG. BernardiniS. Amantadine in Huntington’s disease: Open-label video-blinded study.Neurol. Sci.2002230Suppl. 2s83s8410.1007/s100720200081 12548355
     [Google Scholar]
  39. Huntington Study Group. Dosage effects of riluzole in Huntington’s disease.Neurology200361111551155610.1212/01.WNL.0000096019.71649.2B 14663041
     [Google Scholar]
  40. LandwehrmeyerG.B. DuboisB. de YébenesJ.G. Riluzole in Huntington’s disease: A 3‐year, randomized controlled study.Ann. Neurol.200762326227210.1002/ana.21181 17702031
     [Google Scholar]
  41. O’SuilleabhainP. DeweyR.B.Jr A randomized trial of amantadine in Huntington disease.Arch. Neurol.200360799699810.1001/archneur.60.7.996 12873857
     [Google Scholar]
  42. TestaC.M. JankovicJ. Huntington disease: A quarter century of progress since the gene discovery.J. Neurol. Sci.2019396526810.1016/j.jns.2018.09.022 30419368
     [Google Scholar]
  43. PaulsenJ.S. ButtersN. SadekJ.R. Distinct cognitive profiles of cortical and subcortical dementia in advanced illness.Neurology199545595195610.1212/WNL.45.5.951 7746413
     [Google Scholar]
  44. FernandezH.H. FriedmanJ.H. GraceJ. Beason-HazenS. Donepezil for Huntington’s disease.Mov. Disord.200015117317610.1002/1531‑8257(200001)15:1<173::AID‑MDS1032>3.0.CO;2‑T 10634264
     [Google Scholar]
  45. RotU. KobalJ. SeverA. Pirtošek Z, Mesec A. Rivastigmine in the treatment of Huntington’s disease.Eur. J. Neurol.20029668969010.1046/j.1468‑1331.2002.00447_4.x 12453090
     [Google Scholar]
  46. de TommasoM. SpecchioN. SciruicchioV. DifruscoloO. SpecchioL.M. Effects of rivastigmine on motor and cognitive impairment in Huntington’s disease.Mov. Disord.200419121516151810.1002/mds.20235 15390067
     [Google Scholar]
  47. PetrikisP. AndreouC. PiachasA. BozikasV.P. KaravatosA. Treatment of Huntington??s disease with galantamine.Int. Clin. Psychopharmacol.2004191495010.1097/00004850‑200401000‑00010 15101572
     [Google Scholar]
  48. GaltsC.P.C. BettioL.E.B. JewettD.C. Depression in neurodegenerative diseases: Common mechanisms and current treatment options.Neurosci. Biobehav. Rev.2019102568410.1016/j.neubiorev.2019.04.002 30995512
     [Google Scholar]
  49. van DuijnE. Medical treatment of behavioral manifestations of Huntington disease.Handb. Clin. Neurol.201714412913910.1016/B978‑0‑12‑801893‑4.00011‑0 28947111
     [Google Scholar]
  50. MoultonC.D. HopkinsC.W.P. Bevan-JonesW.R. Systematic review of pharmacological treatments for depressive symptoms in Huntington’s disease.Mov. Disord.201429121556156110.1002/mds.25980 25111961
     [Google Scholar]
  51. PaleacuD. AncaM. GiladiN. Olanzapine in Huntington’s disease.Acta Neurol. Scand.2002105644144410.1034/j.1600‑0404.2002.01197.x 12027832
     [Google Scholar]
  52. NasrallahH.A. BlackD.W. GoldbergJ.F. MuzinaD.J. PariserS.F. Diagnosing and managing psychotic and mood disorders.Ann. Clin. Psychiatry200820Suppl. 1S1S28 19034748
     [Google Scholar]
  53. EddyC.M. ParkinsonE.G. RickardsH.E. Changes in mental state and behaviour in Huntington’s disease.Lancet Psychiatry20163111079108610.1016/S2215‑0366(16)30144‑4 27663851
     [Google Scholar]
  54. AndersonK.E. van DuijnE. CraufurdD. Clinical management of neuropsychiatric symptoms of Huntington disease: Expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders.J. Huntingtons Dis.20187435536610.3233/JHD‑180293 30040737
     [Google Scholar]
  55. van DuijnE. KingmaE.M. van der MastR.C. Psychopathology in verified Huntington’s disease gene carriers.J. Neuropsychiatry Clin. Neurosci.200719444144810.1176/jnp.2007.19.4.441 18070848
     [Google Scholar]
  56. van DuijnE. CraufurdD. HubersA.A.M. Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY).J. Neurol. Neurosurg. Psychiatry201485121411141810.1136/jnnp‑2013‑307343 24828898
     [Google Scholar]
  57. KhodagholiF. MalekiA. MotamediF. MousaviM.A. RafieiS. MoslemiM. 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.20224241105112310.1007/s10571‑020‑01003‑0 33201416
     [Google Scholar]
  58. SimmonsD.A. MassaS.M. Neurotrophin receptor signaling as a therapeutic target for Huntington’s Disease.CNS Neurol. Disord. Drug Targets2017163291302
     [Google Scholar]
  59. DevadigaS.J. BharateS.S. Recent developments in the management of Huntington’s disease.Bioorg. Chem.202212010564210.1016/j.bioorg.2022.105642 35121553
     [Google Scholar]
  60. WheelockV.L. TempkinT. MarderK. Predictors of nursing home placement in Huntington disease.Neurology2003606998100110.1212/01.WNL.0000052992.58107.67 12654967
     [Google Scholar]
  61. VuongK. CanningC.G. MenantJ.C. LoyC.T. Gait, balance, and falls in Huntington disease.Handb. Clin. Neurol.201815925126010.1016/B978‑0‑444‑63916‑5.00016‑1 30482318
     [Google Scholar]
  62. BohlenS EkwallC Hellström K, et al. Physical therapy in H untington’s disease – toward objective assessments?Eur. J. Neurol.201320238939310.1111/j.1468‑1331.2012.03760.x 22672573
     [Google Scholar]
  63. HartmannC.J. GroissS.J. VesperJ. SchnitzlerA. WojteckiL. Brain stimulation in Huntington’s disease.Neurodegener. Dis. Manag.20166322323610.2217/nmt‑2016‑0007 27230813
     [Google Scholar]
  64. GonzalezV. CifL. BiolsiB. Deep brain stimulation for Huntington’s disease: Long-term results of a prospective open-label study.J. Neurosurg.2014121111412210.3171/2014.2.JNS131722 24702329
     [Google Scholar]
  65. CotrimA.P. BaumB.J. Gene therapy: Some history, applications, problems, and prospects.Toxicol. Pathol.20083619710310.1177/0192623307309925 18337227
     [Google Scholar]
  66. IqubalA. IqubalM.K. KhanA. AliJ. BabootaS. HaqueS.E. Gene therapy, a novel therapeutic tool for neurological disorders: Current progress, challenges and future prospective.Curr. Gene Ther.202020318419410.2174/1566523220999200716111502 32674730
     [Google Scholar]
  67. CostantiniL.C. BakowskaJ.C. BreakefieldX.O. IsacsonO. Gene therapy in the CNS.Gene Ther.2000729310910.1038/sj.gt.3301119 10673714
     [Google Scholar]
  68. WijekoonN. GonawalaL. RatnayakeP. Gene therapy for selected neuromuscular and trinucleotide repeat disorders – An insight to subsume South Asia for multicenter clinical trials.IBRO Neuroscience Reports20231414615310.1016/j.ibneur.2023.01.009 36819775
     [Google Scholar]
  69. SladeN. Viral vectors in gene therapy.Period. Biol.20011032139144
     [Google Scholar]
  70. SimonatoM. BennettJ. BoulisN.M. Progress in gene therapy for neurological disorders.Nat. Rev. Neurol.20139527729110.1038/nrneurol.2013.56 23609618
     [Google Scholar]
  71. BoulaizH. MarchalJ.A. PradosJ. MelguizoC. Aránega A. Non-viral and viral vectors for gene therapy.Cell. Mol. Biol.2005511322 16171561
     [Google Scholar]
  72. ArnedoA. IracheJ.M. MerodioM. Millán, MS. Albumin nanoparticles improved the stability, nuclear accumulation and anticytomegaloviral activity of a phosphodiester oligonucleotide.J. Control. Release200494121722710.1016/j.jconrel.2003.10.009 14684285
     [Google Scholar]
  73. LvH. ZhangS. WangB. CuiS. YanJ. Toxicity of cationic lipids and cationic polymers in gene delivery.J. Control. Release2006114110010910.1016/j.jconrel.2006.04.014 16831482
     [Google Scholar]
  74. IbraheemD. ElaissariA. FessiH. Gene therapy and DNA delivery systems.Int. J. Pharm.20144591-2708310.1016/j.ijpharm.2013.11.041 24286924
     [Google Scholar]
  75. YamamotoA. LucasJ.J. HenR. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease.Cell20001011576610.1016/S0092‑8674(00)80623‑6 10778856
     [Google Scholar]
  76. LeeC.Y.D. CantleJ.P. YangX.W. Genetic manipulations of mutant huntingtin in mice: New insights into Huntington’s disease pathogenesis.FEBS J.2013280184382439410.1111/febs.12418 23829302
     [Google Scholar]
  77. MiniarikovaJ. EversM.M. KonstantinovaP. Translation of microRNA-based huntingtin-lowering therapies from preclinical studies to the clinic.Mol. Ther.201826494796210.1016/j.ymthe.2018.02.002 29503201
     [Google Scholar]
  78. TabriziS.J. LeavittB.R. LandwehrmeyerG.B. Targeting huntingtin expression in patients with Huntington’s disease.N. Engl. J. Med.2019380242307231610.1056/NEJMoa1900907 31059641
     [Google Scholar]
  79. RinaldiC. WoodM.J.A. Antisense oligonucleotides: The next frontier for treatment of neurological disorders.Nat. Rev. Neurol.201814192110.1038/nrneurol.2017.148 29192260
     [Google Scholar]
  80. KordasiewiczH.B. StanekL.M. WancewiczE.V. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis.Neuron20127461031104410.1016/j.neuron.2012.05.009 22726834
     [Google Scholar]
  81. CarrollJ.B. WarbyS.C. SouthwellA.L. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene/allele-specific silencing of mutant huntingtin.Mol. Ther.201119122178218510.1038/mt.2011.201 21971427
     [Google Scholar]
  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 Res2013412196345010.1093/nar/gkt725 23963702
     [Google Scholar]
  83. BečanovićK. NørremølleA. NealS.J. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.Nat. Neurosci.201518680781610.1038/nn.4014 25938884
     [Google Scholar]
  84. AguiarS. van der GaagB. CorteseF.A.B. RNAi mechanisms in Huntington’s disease therapy: siRNA versus shRNA.Transl. Neurodegener.2017613010.1186/s40035‑017‑0101‑9 29209494
     [Google Scholar]
  85. RookM.E. SouthwellA.L. Antisense oligonucleotide therapy: From design to the Huntington disease clinic.BioDrugs202236210511910.1007/s40259‑022‑00519‑9 35254632
     [Google Scholar]
  86. TabriziS.J. Estevez-FragaC. van Roon-MomW.M.C. Potential disease-modifying therapies for Huntington’s disease: Lessons learned and future opportunities.Lancet Neurol.202221764565810.1016/S1474‑4422(22)00121‑1 35716694
     [Google Scholar]
  87. ByunS. LeeM. KimM. Gene therapy for Huntington’s disease: The final strategy for a cure?J. Mov. Disord.2022151152010.14802/jmd.21006 34781633
     [Google Scholar]
  88. PeplowP.V. MartinezB. Altered microRNA expression in animal models of Huntington’s disease and potential therapeutic strategies.Neural Regen. Res.202116112159216910.4103/1673‑5374.310673 33818488
     [Google Scholar]
  89. RodriguesF.B. WildE.J. Huntington’s disease clinical trials corner: April 2020.J. Huntingtons Dis.20209218519710.3233/JHD‑200002 32250312
     [Google Scholar]
  90. ShannonK.M. Recent Advances in the treatment of Huntington’s Disease: Targeting DNA and RNA.CNS Drugs202034321922810.1007/s40263‑019‑00695‑3 31933283
     [Google Scholar]
  91. CaronN.S. DorseyE.R. HaydenM.R. Therapeutic approaches to Huntington disease: From the bench to the clinic.Nat. Rev. Drug Discov.2018171072975010.1038/nrd.2018.133 30237454
     [Google Scholar]
  92. ZeitlerB. FroelichS. MarlenK. Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease.Nat. Med.20192571131114210.1038/s41591‑019‑0478‑3 31263285
     [Google Scholar]
  93. WildE.J. TabriziS.J. Therapies targeting DNA and RNA in Huntington’s disease.Lancet Neurol.2017161083784710.1016/S1474‑4422(17)30280‑6 28920889
     [Google Scholar]
  94. JiangF. DoudnaJ.A. CRISPR–Cas9 structures and mechanisms.Annu. Rev. Biophys.201746150552910.1146/annurev‑biophys‑062215‑010822 28375731
     [Google Scholar]
  95. LiangP. XuY. ZhangX. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes.Protein Cell20156536337210.1007/s13238‑015‑0153‑5 25894090
     [Google Scholar]
  96. ShinJ.W. KimK.H. ChaoM.J. Permanent inactivation of Huntington’s disease mutation by personalized allele-specific CRISPR/Cas9.Hum. Mol. Genet.20162520ddw28610.1093/hmg/ddw286 28172889
     [Google Scholar]
  97. AlkanliS.S. AlkanliN. AyA. AlbenizI. CRISPR/Cas9 mediated therapeutic approach in Huntington’s disease.Mol. Neurobiol.20236031486149810.1007/s12035‑022‑03150‑5 36482283
     [Google Scholar]
  98. AlpaughM. GalleguillosD. ForeroJ. Disease‐modifying effects of ganglioside GM1 in Huntington’s disease models.EMBO Mol. Med.20179111537155710.15252/emmm.201707763 28993428
     [Google Scholar]
  99. MaglioneV. MarchiP. Di PardoA. Impaired ganglioside metabolism in Huntington’s disease and neuroprotective role of GM1.J. Neurosci.201030114072408010.1523/JNEUROSCI.6348‑09.2010 20237277
     [Google Scholar]
  100. Di PardoA. MaglioneV. AlpaughM. Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice.Proc. Natl. Acad. Sci. USA201210993528353310.1073/pnas.1114502109 22331905
     [Google Scholar]
  101. Sadri-VakiliG. ChaJ.H.J. Mechanisms of Disease: Histone modifications in Huntington’s disease.Nat. Clin. Pract. Neurol.20062633033810.1038/ncpneuro0199 16932577
     [Google Scholar]
  102. SüssmuthS.D. HaiderS. LandwehrmeyerG.B. An exploratory double‐blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntington’s disease.Br. J. Clin. Pharmacol.201579346547610.1111/bcp.12512 25223731
     [Google Scholar]
  103. CardinaleA. FuscoF.R. Inhibition of phosphodiesterases as a strategy to achieve neuroprotection in Huntington’s disease.CNS Neurosci. Ther.201824431932810.1111/cns.12834 29500937
     [Google Scholar]
  104. HebbA.L.O. RobertsonH.A. Denovan-WrightE.M. Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington′s disease transgenic mice prior to the onset of motor symptoms.Neuroscience2004123496798110.1016/j.neuroscience.2003.11.009 14751289
     [Google Scholar]
  105. GiraltA SaavedraA Carretón O, et al. PDE10 inhibition increases GluA1 and CREB phosphorylation and improves spatial and recognition memories in a Huntington’s disease mouse model.Hippocampus201323868469510.1002/hipo.22128 23576401
     [Google Scholar]
  106. GinésS. BoschM. MarcoS. Reduced expression of the TrkB receptor in Huntington’s disease mouse models and in human brain.Eur. J. Neurosci.200623364965810.1111/j.1460‑9568.2006.04590.x 16487146
     [Google Scholar]
  107. ToddD. GowersI. DowlerS.J. A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington’s disease.PLoS One201492e8792310.1371/journal.pone.0087923 24503862
     [Google Scholar]
  108. ThevandavakkamM.A. SchwarczR. MuchowskiP.J. GiorginiF. Targeting kynurenine 3-monooxygenase (KMO): Implications for therapy in Huntington’s disease.CNS Neurol. Disord. Drug Targets20109679180010.2174/187152710793237430 20942784
     [Google Scholar]
  109. CampesanS. GreenE.W. BredaC. The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington’s disease.Curr. Biol.2011211196196610.1016/j.cub.2011.04.028 21636279
     [Google Scholar]
  110. JiaH. WangY. MorrisC.D. The effects of pharmacological inhibition of Histone Deacetylase 3 (HDAC3) in Huntington’s Disease mice.PLoS One2016113e015249810.1371/journal.pone.0152498 27031333
     [Google Scholar]
  111. FerranteR.J. KubilusJ.K. LeeJ. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington’s disease mice.J. Neurosci.200323289418942710.1523/JNEUROSCI.23‑28‑09418.2003 14561870
     [Google Scholar]
  112. RavikumarB. ImarisioS. SarkarS. O’KaneC.J. RubinszteinD.C. Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease.J. Cell Sci.2008121101649166010.1242/jcs.025726 18430781
     [Google Scholar]
  113. FoxL.M. KimK. JohnsonC.W. Huntington’s Disease pathogenesis is modified in vivo by Alfy/Wdfy3 and selective macroautophagy.Neuron20201055813821.e610.1016/j.neuron.2019.12.003 31899071
     [Google Scholar]
  114. MonkR. ConnorB. Cell replacement therapy for Huntington’s Disease.Adv. Exp. Med. Biol.20201266576910.1007/978‑981‑15‑4370‑8_5 33105495
     [Google Scholar]
  115. TartaglioneA.M. PopoliP. CalamandreiG. Regenerative medicine in Huntington’s disease: Strengths and weaknesses of preclinical studies.Neurosci. Biobehav. Rev.201777324710.1016/j.neubiorev.2017.02.017 28223129
     [Google Scholar]
  116. CarriA.D. OnoratiM. LelosM.J. Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons.Development2013140230131210.1242/dev.084608 23250204
     [Google Scholar]
  117. ArberC. PreciousS.V. CambrayS. Activin A directs striatal projection neuron differentiation of human pluripotent stem cells.Development201514271375138610.1242/dev.117093 25804741
     [Google Scholar]
  118. FaedoA. LaportaA. SegnaliA. Differentiation of human telencephalic progenitor cells into MSNs by inducible expression of Gsx2 and Ebf1.Proc. Natl. Acad. Sci. USA20171147E1234E124210.1073/pnas.1611473114 28137879
     [Google Scholar]
  119. KendallA.L. RaymentF.D. TorresE.M. BakerH.F. RidleyR.M. DunnettS.B. Functional integration of striatal allografts in a primate model of Huntington’s disease.Nat. Med.19984672772910.1038/nm0698‑727 9623985
     [Google Scholar]
  120. DunnettS.B. NathwaniF. Björklund A. The integration and function of striatal grafts.Prog Brain Res20001273458010.1016/S0079‑6123(00)27017‑9 11142035
     [Google Scholar]
  121. DeckelA.W. MoranT.H. CoyleJ.T. SanbergP.R. RobinsonR.G. Anatomical predictors of behavioral recovery following fetal striatal transplants.Brain Res.1986365224925810.1016/0006‑8993(86)91636‑7 3947993
     [Google Scholar]
  122. IsacsonO. DunnettS.B. BjörklundA. Graft-induced behavioral recovery in an animal model of Huntington disease.Proc. Natl. Acad. Sci. USA19868382728273210.1073/pnas.83.8.2728 2939457
     [Google Scholar]
  123. PritzelM. IsacsonO. BrundinP. WiklundL. BjörklundA. Afferent and efferent connections of striatal grafts implanted into the ibotenic acid lesioned neostriatum in adult rats.Exp. Brain Res.198665111212610.1007/BF00243834 2433142
     [Google Scholar]
  124. SirinathsinghjiD.J.S. DunnettS.B. IsacsonO. ClarkeD.J. KendrickK. BjörklundA. Striatal grafts in rats with unilateral neostriatal lesions—II. In vivo monitoring of gaba release in globus pallidus and substantia nigra.Neuroscience198824380381110.1016/0306‑4522(88)90068‑1 3380300
     [Google Scholar]
  125. ClarkeD.J. DunnettS.B. IsacsonO. Björklund A. Striatal grafts in the ibotenic acid-lesioned neostriatum: Ultrastructural and immunocytochemical studies. Prog Brain Res198878475310.1016/S0079‑6123(08)60265‑4 3247443
     [Google Scholar]
  126. ClarkeD.J. DunnettS.B. IsacsonO. SirinathsinghjiD.J.S. BjörklundA. Striatal grafts in rats with unilateral neostriatal lesions—I. Ultrastructural evidence of afferent synaptic inputs from the host nigrostriatal pathway.Neuroscience198824379180110.1016/0306‑4522(88)90067‑X 2898109
     [Google Scholar]
  127. DunnettS.B. IsacsonO. SirinathsinghjiD.J.S. ClarkeD.J. BjörklundA. Striatal grafts in rats with unilateral neostriatal lesions—III. Recovery from dopamine-dependent motor asymmetry and deficits in skilled paw reaching.Neuroscience198824381382010.1016/0306‑4522(88)90069‑3 3380301
     [Google Scholar]
  128. DunnettS.B. IsacsonO. SirinathsinghjiD.J.S. ClarkeD.J. Björklund A. Striatal grafts in the ibotenic acid-lesioned neostriatum: Functional studies.Prog Brain Res198878394510.1016/S0079‑6123(08)60264‑2 3073422
     [Google Scholar]
  129. PalfiS. CondéF. RicheD. Fetal striatal allografts reverse cognitive deficits in a primate model of Huntington disease.Nat. Med.19984896396610.1038/nm0898‑963 9701252
     [Google Scholar]
  130. NakaoN. ItakuraT. Fetal tissue transplants in animal models of Huntington’s disease: The effects on damaged neuronal circuitry and behavioral deficits.Prog. Neurobiol.200061331333810.1016/S0301‑0082(99)00058‑1 10727778
     [Google Scholar]
  131. FreemanT.B. HauserR.A. WillingA.E. ZigovaT. SanbergP.R. SaportaS. Transplantation of human fetal striatal tissue in Huntington’s disease: Rationale for clinical studies.Novartis Found. Symp.200023112913810.1002/0470870834.ch8 11131535
     [Google Scholar]
  132. KleinA. LaneE.L. DunnettS.B. Brain repair in a unilateral rat model of Huntington’s disease: New insights into impairment and restoration of forelimb movement patterns.Cell Transplant.201322101735175110.3727/096368912X657918 23067670
     [Google Scholar]
  133. CisbaniG. Saint-PierreM. CicchettiF. Single-cell suspension methodology favors survival and vascularization of fetal striatal grafts in the YAC128 mouse model of Huntington’s disease.Cell Transplant.201423101267127810.3727/096368913X668636 23768945
     [Google Scholar]
  134. Bachoud-LéviA.C. Human fetal cell therapy in Huntington’s Disease: A randomized, multicenter, phase II trial.Mov. Disord.20203581323133510.1002/mds.28201 32666599
     [Google Scholar]
  135. ArnholdS. LenartzD. KruttwigK. 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.20009361026103210.3171/jns.2000.93.6.1026 11117845
     [Google Scholar]
  136. NasonkinI. MahairakiV. XuL. Long-term, stable differentiation of human embryonic stem cell-derived neural precursors grafted into the adult mammalian neostriatum.Stem Cells200927102414242610.1002/stem.177 19609935
     [Google Scholar]
  137. NiwaH. MiyazakiJ. SmithA.G. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.Nat. Genet.200024437237610.1038/74199 10742100
     [Google Scholar]
  138. ChambersI. ColbyD. RobertsonM. NicholsJ. LeeS. TweedieS. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells.Cell2003113564365510.1016/S0092‑8674(03)00392‑1 12787505
     [Google Scholar]
  139. ChewJ.L. LohY.H. ZhangW. Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells.Mol. Cell. Biol.200525146031604610.1128/MCB.25.14.6031‑6046.2005 15988017
     [Google Scholar]
  140. MichelsenK.A. Acosta-VerdugoS. Benoit-MarandM. Area-specific reestablishment of damaged circuits in the adult cerebral cortex by cortical neurons derived from mouse embryonic stem cells.Neuron201585598299710.1016/j.neuron.2015.02.001 25741724
     [Google Scholar]
  141. TakahashiK. YamanakaS. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell2006126466367610.1016/j.cell.2006.07.024 16904174
     [Google Scholar]
  142. ParkI.H. AroraN. HuoH. Disease-specific induced pluripotent stem cells.Cell2008134587788610.1016/j.cell.2008.07.041 18691744
     [Google Scholar]
  143. ZhangN. AnM.C. MontoroD. EllerbyL.M. Characterization of human Huntington’s disease cell model from induced pluripotent stem cells.PLoS Curr.20102RRN119310.1371/currents.RRN1193 21037797
     [Google Scholar]
  144. ChaeJ.I. KimD.W. LeeN. Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington’s disease patient.Biochem. J.2012446335937110.1042/BJ20111495 22694310
     [Google Scholar]
  145. JeonI. LeeN. LiJ.Y. Neuronal properties, in vivo effects, and pathology of a Huntington’s disease patient-derived induced pluripotent stem cells.Stem Cells20123092054206210.1002/stem.1135 22628015
     [Google Scholar]
  146. JeonI. ChoiC. LeeN. 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 Cells201471434710.15283/ijsc.2014.7.1.43 24921027
     [Google Scholar]
  147. AnM.C. ZhangN. ScottG. Genetic correction of Huntington’s disease phenotypes in induced pluripotent stem cells.Cell Stem Cell201211225326310.1016/j.stem.2012.04.026 22748967
     [Google Scholar]
  148. KerkisI. HaddadM.S. ValverdeC.W. GlosmanS. Neural and mesenchymal stem cells in animal models of Huntington’s disease: Past experiences and future challenges.Stem Cell Res. Ther.20156123210.1186/s13287‑015‑0248‑1 26667114
     [Google Scholar]
  149. BantubungiK. BlumD. CuvelierL. Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington’s disease.Mol. Cell. Neurosci.200837345447010.1016/j.mcn.2007.11.001 18083596
     [Google Scholar]
  150. SnyderB.R. ChiuA.M. ProckopD.J. ChanA.W.S. Human multipotent stromal cells (MSCs) increase neurogenesis and decrease atrophy of the striatum in a transgenic mouse model for Huntington’s disease.PLoS One201052e934710.1371/journal.pone.0009347 20179764
     [Google Scholar]
  151. FinkK.D. RossignolJ. CraneA.T. Transplantation of umbilical cord-derived mesenchymal stem cells into the striata of R6/2 mice: Behavioral and neuropathological analysis.Stem Cell Res. Ther.20134513010.1186/scrt341 24456799
     [Google Scholar]
  152. LeeS.T. ChuK. JungK.H. Slowed progression in models of huntington disease by adipose stem cell transplantation.Ann. Neurol.200966567168110.1002/ana.21788 19938161
     [Google Scholar]
  153. LinY.T. ChernY. ShenC.K.J. Human mesenchymal stem cells prolong survival and ameliorate motor deficit through trophic support in Huntington’s disease mouse models.PLoS One201168e2292410.1371/journal.pone.0022924 21850243
     [Google Scholar]
  154. MoraesL. Vasconcelos-dos-SantosA. SantanaF.C. 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.)20129214315510.1016/j.scr.2012.05.005 22742973
     [Google Scholar]
  155. JiangY. LvH. HuangS. TanH. ZhangY. LiH. Bone marrow mesenchymal stem cells can improve the motor function of a Huntington’s disease rat model.Neurol. Res.201133333133710.1179/016164110X12816242542571 21513650
     [Google Scholar]
  156. RossignolJ. BoyerC. LévèqueX. Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington’s disease: Morphological and behavioral outcomes.Behav. Brain Res.2011217236937810.1016/j.bbr.2010.11.006 21070819
     [Google Scholar]
  157. MullenR.J. BuckC.R. SmithA.M. NeuN, a neuronal specific nuclear protein in vertebratesxs.Development1992116120121110.1242/dev.116.1.201 1483388
     [Google Scholar]
  158. LiangX.S. SunZ.W. ThomasA.M. LiS. Mesenchymal stem cell therapy for Huntington Disease: A meta-analysis.Stem Cells Int.20232023116110996710.1155/2023/1109967
     [Google Scholar]
  159. RossignolJ. FinkK. DavisK. Transplants of adult mesenchymal and neural stem cells provide neuroprotection and behavioral sparing in a transgenic rat model of Huntington’s disease.Stem Cells201432250050910.1002/stem.1508 23939879
     [Google Scholar]
  160. ChoiK.A. HongS. Induced neural stem cells as a means of treatment in Huntington’s disease.Expert Opin. Biol. Ther.2017171111110.1080/14712598.2017.1365133 28792249
     [Google Scholar]
  161. NakaoN. OguraM. NakaiK. ItakuraT. Embryonic striatal grafts restore neuronal activity of the globus pallidus in a rodent model of Huntington’s disease.Neuroscience199988246947710.1016/S0306‑4522(98)00197‑3 10197767
     [Google Scholar]
  162. YangC.R. YuR.K. Intracerebral transplantation of neural stem cells combined with trehalose ingestion alleviates pathology in a mouse model of Huntington’s disease.J. Neurosci. Res.2009871263310.1002/jnr.21817 18683244
     [Google Scholar]
  163. AubryL. BugiA. LefortN. RousseauF. PeschanskiM. PerrierA.L. Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats.Proc. Natl. Acad. Sci. USA200810543167071671210.1073/pnas.0808488105 18922775
     [Google Scholar]
  164. McBrideJ.L. BehrstockS.P. ChenE.Y. Human neural stem cell transplants improve motor function in a rat model of Huntington’s disease.J. Comp. Neurol.2004475221121910.1002/cne.20176 15211462
     [Google Scholar]
  165. JohannV. SchieferJ. SassC. Time of transplantation and cell preparation determine neural stem cell survival in a mouse model of Huntington’s disease.Exp. Brain Res.2007177445847010.1007/s00221‑006‑0689‑y 17013619
     [Google Scholar]
  166. RyuJ.K. KimJ. ChoS.J. Proactive transplantation of human neural stem cells prevents degeneration of striatal neurons in a rat model of Huntington disease.Neurobiol. Dis.2004161687710.1016/j.nbd.2004.01.016 15207263
     [Google Scholar]
  167. ClinicalTrials.gov.Available Fromwww.clinicaltrials.gov
     [Google Scholar]
  168. RosserA.E. BusseM.E. GrayW.P. Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder.Brain202214551584159710.1093/brain/awac086 35262656
     [Google Scholar]
  169. PuhlD.L. D’AmatoA.R. GilbertR.J. Challenges of gene delivery to the central nervous system and the growing use of biomaterial vectors.Brain Res. Bull.201915021623010.1016/j.brainresbull.2019.05.024 31173859
     [Google Scholar]
  170. PiguetF. de Saint DenisT. AudouardE. The challenge of gene therapy for neurological diseases: Strategies and tools to achieve efficient delivery to the central nervous system.Hum. Gene Ther.2021327-834937410.1089/hum.2020.105 33167739
     [Google Scholar]
  171. LelosM.J. Investigating cell therapies in animal models of Parkinson’s and Huntington’s disease: Current challenges and considerations. International Review of Neurobiology.AmsterdamElsevier2022159189
     [Google Scholar]
  172. ShenF. FanY. SuH. Adeno-associated viral vector-mediated hypoxia-regulated VEGF gene transfer promotes angiogenesis following focal cerebral ischemia in mice.Gene Ther.2008151303910.1038/sj.gt.3303048 17960159
     [Google Scholar]
  173. SmithK.R. Gene therapy: The potential applicability of gene transfer technology to the human germline.Int. J. Med. Sci.200412769110.7150/ijms.1.76 15912200
     [Google Scholar]
  174. GoreM.E. Adverse effects of gene therapy: Gene therapy can cause leukaemia: No shock, mild horror but a probe.Gene Ther.2003101410.1038/sj.gt.3301946
     [Google Scholar]
  175. ThrasherA.J. WilliamsD.A. Evolving gene therapy in primary immunodeficiency.Mol. Ther.20172551132114110.1016/j.ymthe.2017.03.018 28366768
     [Google Scholar]
  176. PenaS.A. IyengarR. EshraghiR.S. Gene therapy for neurological disorders: Challenges and recent advancements.J. Drug Target.202028211112810.1080/1061186X.2019.1630415 31195838
     [Google Scholar]
  177. ThomasC.E. EhrhardtA. KayM.A. Progress and problems with the use of viral vectors for gene therapy.Nat. Rev. Genet.20034534635810.1038/nrg1066 12728277
     [Google Scholar]
  178. Alvarez-ErvitiL. SeowY. YinH. BettsC. LakhalS. WoodM.J.A. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.Nat. Biotechnol.201129434134510.1038/nbt.1807 21423189
     [Google Scholar]
  179. FanC.H. TingC.Y. LinC.Y. Noninvasive, Targeted and Non-Viral Ultrasound-Mediated GDNF-Plasmid Delivery for Treatment of Parkinson’s Disease.Sci. Rep.2016611957910.1038/srep19579 26786201
     [Google Scholar]
  180. LiY. WangJ. LeeC.G.L. 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.200411110911410.1038/sj.gt.3302135 14681704
     [Google Scholar]
  181. JoshiC.R. LabhasetwarV. GhorpadeA. Destination brain: The past, present, and future of therapeutic gene delivery.J. Neuroimmune Pharmacol.2017121518310.1007/s11481‑016‑9724‑3 28160121
     [Google Scholar]
  182. van TellingenO. Yetkin-ArikB. de GooijerM.C. WesselingP. WurdingerT. de VriesH.E. Overcoming the blood–brain tumor barrier for effective glioblastoma treatment.Drug Resist. Updat.20151911210.1016/j.drup.2015.02.002 25791797
     [Google Scholar]
  183. KoltoverI. SaldittT. RädlerJO. SafinyaCR. An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery.Science19982815373788110.1126/science.281.5373.78 9651248
     [Google Scholar]
  184. KumarP. WuH. McBrideJ.L. Transvascular delivery of small interfering RNA to the central nervous system.Nature20074487149394310.1038/nature05901 17572664
     [Google Scholar]
  185. FogedC. NielsenH.M. Cell-penetrating peptides for drug delivery across membrane barriers.Expert Opin. Drug Deliv.20085110511710.1517/17425247.5.1.105 18095931
     [Google Scholar]
  186. Salado-ManzanoC Perpiña U, Straccia M, et al. Is the immunological response a bottleneck for cell therapy in neurodegenerative diseases?Front. Cell. Neurosci.20201425010.3389/fncel.2020.00250 32848630
     [Google Scholar]
  187. DrewC.J.G. BusseM. Considerations for clinical trial design and conduct in the evaluation of novel advanced therapeutics in neurodegenerative disease. International Review of Neurobiology.AmsterdamElsevier2022235279
     [Google Scholar]
  188. European Medicines Agency. Guideline on human cell-based medicinal products.2008Available 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.2015Available 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.2003Available From https://www.fda.gov/media/73624/download
  191. Food and Drug Administration. Proposed approach to regulation of cellular and tissue-based products.1997Available 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.2010Available 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.2008Available 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
     [Google Scholar]
  195. KlugB. ReinhardtJ. SchröderC. Requirements for long-term follow-up on efficacy and safety of advanced therapy medicinal products.Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz2010531586210.1007/s00103‑009‑0992‑4 19949763
     [Google Scholar]
  196. HarperS.Q. StaberP.D. HeX. RNA interference improves motor and neuropathological abnormalities in a Huntington’s disease mouse model.Proc. Natl. Acad. Sci. USA2005102165820582510.1073/pnas.0501507102 15811941
     [Google Scholar]
  197. EkmanF.K. OjalaD.S. AdilM.M. LopezP.A. SchafferD.V. GajT. CRISPR-Cas9-mediated genome editing increases lifespan and improves motor deficits in a Huntington’s disease mouse model.Mol. Ther. Nucleic Acids20191782983910.1016/j.omtn.2019.07.009 31465962
     [Google Scholar]
  198. ChenW. HuY. JuD. Gene therapy for neurodegenerative disorders: Aadvances, insights and prospects.Acta Pharm. Sin. B20201081347135910.1016/j.apsb.2020.01.015 32963936
     [Google Scholar]
  199. TabriziS.J. GhoshR. LeavittB.R. Huntingtin lowering strategies for disease modification in Huntington’s disease.Neuron2019101580181910.1016/j.neuron.2019.01.039 30844400
     [Google Scholar]
  200. BeatrizM. LopesC. RibeiroA.C.S. RegoA.C.C. Revisiting cell and gene therapies in Huntington’s disease.J. Neurosci. Res.20219971744176210.1002/jnr.24845 33881180
     [Google Scholar]
  201. KerkisI. AraldiR.P. WenceslauC.V. MendesT.B. Advances in cellular and cell-free therapy medicinal products for Huntington disease treatment.From Pathophysiology to Treatment of Huntington’s Disease.LondonIntechOpen202210.5772/intechopen.102539
     [Google Scholar]
  202. ConnerL.T. SrinageshwarB. BakkeJ.L. DunbarG.L. RossignolJ. Advances in stem cell and other therapies for Huntington’s disease: An update.Brain Res. Bull.202319911067310.1016/j.brainresbull.2023.110673 37257627
     [Google Scholar]
  203. DuanW. UraniE. MattsonM.P. The potential of gene editing for Huntington’s disease.Trends Neurosci.202346536537610.1016/j.tins.2023.02.005 36907678
     [Google Scholar]
  204. Bachoud-LéviA.C. MassartR. RosserA. Cell therapy in Huntington’s disease: Taking stock of past studies to move the field forward.Stem Cells202139214415510.1002/stem.3300 33176057
     [Google Scholar]
/content/journals/crcep/10.2174/0127724328300166240510071548
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Translational Approach using Advanced Therapy Medicinal Products for Huntington's Disease
Curr Rev Clin Exper Pharm 20, 14 (2025); https://doi.org/10.2174/0127724328300166240510071548
/content/journals/crcep/10.2174/0127724328300166240510071548
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  • Article Type:     Review Article
Keyword(s): Advanced therapy medicinal products; ATMP; cell therapy; gene therapy; huntington's disease; RNAs

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