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Huntington’s Disease—Update on Treatments

  • Movement Disorders (S Fox, Section Editor)
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Abstract

Huntington’s disease (HD) is an autosomal dominantly inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, ending in death. Despite the discovery of the underlying genetic mutation more than 20 years ago, treatment remains focused on symptomatic management. Chorea, the most recognizable symptom, responds to medication that reduces dopaminergic neurotransmission. Psychiatric symptoms such as depression and anxiety may also respond well to symptomatic therapies. Unfortunately, many other symptoms do not respond to current treatments. Furthermore, high-quality evidence for treatment of HD in general remains limited. To date, there has been minimal success with identifying a disease-modifying therapy based upon molecular models. However, one of the emerging gene silencing techniques may provide a breakthrough in treating this devastating disease.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance

  1. Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72(6):971–83.

    Article  Google Scholar 

  2. Deng YP, et al. Differential loss of striatal projection systems in Huntington’s disease: a quantitative immunohistochemical study. J Chem Neuroanat. 2004;27(3):143–64.

    Article  CAS  PubMed  Google Scholar 

  3. Reiner A, et al. Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci. 1988;85(15):5733–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hayden MR, et al. Tetrabenazine. Nat Rev Drug Discov. 2009;8(1):17–8.

    Article  CAS  PubMed  Google Scholar 

  5. Mehanna R, et al. Analysis of CYP2D6 genotype and response to tetrabenazine. Mov Disord. 2013;28(2):210–5.

    Article  CAS  PubMed  Google Scholar 

  6. Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord. 2007;22(2):193–7.

    Article  PubMed  Google Scholar 

  7. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006;66(3):366–72.

    Article  CAS  Google Scholar 

  8. Frank S. Huntington Study Group/TETRA-HD investigators. Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study BMC Neurol. 2009;9:62.

    PubMed  Google Scholar 

  9. Fasano A, et al. The long-term effect of tetrabenazine in the management of Huntington disease. Clin Neuropharmacol. 2008;31(6):313–8.

    Article  CAS  PubMed  Google Scholar 

  10. Frank S, et al. A study of chorea after tetrabenazine withdrawal in patients with Huntington disease. Clin Neuropharmacol. 2008;31(3):127–33.

    Article  CAS  PubMed  Google Scholar 

  11. Shen V, et al. Safety and efficacy of tetrabenazine and use of concomitant medications during long-term, open-label treatment of chorea associated with Huntington’s and other diseases. Tremor Other Hyperkinet Mov. 2013;3

  12. Dorsey ER, et al. Depressed mood and suicidality in individuals exposed to tetrabenazine in a large Huntington disease observational study. J Huntingtons Dis. 2013;2(4):509–15.

    CAS  PubMed  Google Scholar 

  13. •• Frank S, et al. Effect of deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA. 2016;316(1):40–50. A recent trial testing a novel molecule containing deuterium bound to tetrabenazine (TBZ), used to prolong the half-life of TBZ and decrease the side effects. This new medication could potentially allow for better control of chorea with fewer side effects

    Article  CAS  PubMed  Google Scholar 

  14. Leonard DP, et al. Letter: double-blind trial of lithium carbonate and haloperidol in Huntington’s chorea. Lancet. 1974;2(7890):1208–9.

    Article  CAS  PubMed  Google Scholar 

  15. Shoulson I. Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs. Neurology. 1981;31(10):1333–5.

    Article  CAS  PubMed  Google Scholar 

  16. Arena R, et al. Huntington’s disease: clinical effects of a short-term treatment with pimozide. Adv Biochem Psychopharmacol. 1980;24:573–5.

    CAS  PubMed  Google Scholar 

  17. Terrence CF. Fluphenazine decanoate in the treatment of chorea: a double-blind study. Curr Ther Res Clin Exp. 1976;20(2):177–83.

    CAS  PubMed  Google Scholar 

  18. van Vugt JP, et al. Clozapine versus placebo in Huntington’s disease: a double blind randomised comparative study. J Neurol Neurosurg Psychiatry. 1997;63(1):35–9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bonuccelli U, et al. Clozapine in Huntington’s chorea. Neurology. 1994;44(5):821–3.

    Article  CAS  PubMed  Google Scholar 

  20. Bonelli RM, Mahnert FA, Niederwieser G. Olanzapine for Huntington’s disease: an open label study. Clin Neuropharmacol. 2002;25(5):263–5.

    Article  CAS  PubMed  Google Scholar 

  21. Paleacu D, Anca M, Giladi N. Olanzapine in Huntington’s disease. Acta Neurol Scand. 2002;105(6):441–4.

    Article  CAS  PubMed  Google Scholar 

  22. Squitieri F, et al. Short-term effects of olanzapine in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(1):69–72.

    CAS  PubMed  Google Scholar 

  23. Brusa L, et al. Treatment of the symptoms of Huntington’s disease: preliminary results comparing aripiprazole and tetrabenazine. Mov Disord. 2009;24(1):126–9.

    Article  PubMed  Google Scholar 

  24. Cankurtaran ES, et al. Clinical experience with risperidone and memantine in the treatment of Huntington’s disease. J Natl Med Assoc. 2006;98(8):1353–5.

    PubMed  PubMed Central  Google Scholar 

  25. Erdemoglu AK, Boratav C. Risperidone in chorea and psychosis of Huntington’s disease. Eur J Neurol. 2002;9(2):182–3.

    Article  PubMed  Google Scholar 

  26. Parsa MA, et al. Risperidone in treatment of choreoathetosis of Huntington’s disease. J Clin Psychopharmacol. 1997;17(2):134–5.

    Article  CAS  PubMed  Google Scholar 

  27. Bonelli RM, Niederwieser G. Quetiapine in Huntington’s disease: a first case report. J Neurol. 2002;249(8):1114–5.

    Article  PubMed  Google Scholar 

  28. Bonelli RM, et al. Ziprasidone in Huntington’s disease: the first case reports. J Psychopharmacol. 2003;17(4):459–60.

    Article  PubMed  Google Scholar 

  29. Lundin A, et al. Efficacy and safety of the dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington’s disease. Clin Neuropharmacol. 2010;33(5):260–4.

    Article  CAS  PubMed  Google Scholar 

  30. de Yebenes JG, et al. Pridopidine for the treatment of motor function in patients with Huntington’s disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011;10(12):1049–57.

    Article  PubMed  CAS  Google Scholar 

  31. Huntington Study Group. A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington’s disease. Mov Disord. 2013;28(10):1407–15.

    Article  CAS  Google Scholar 

  32. Lucetti C, et al. IV amantadine improves chorea in Huntington,s disease: an acute randomized, controlled study. Neurology. 2003;60(12):1995–7.

    Article  CAS  PubMed  Google Scholar 

  33. Lucetti C, et al. Amantadine in Huntington’s disease: open-label video-blinded study. Neurol Sci. 2002;23(Suppl 2):S83–4.

    Article  PubMed  Google Scholar 

  34. Verhagen ML, et al. Huntington’s disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002;59(5):694–9.

    Article  Google Scholar 

  35. O’Suilleabhain P, Dewey RB. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003;60(7):996–8.

    Article  PubMed  Google Scholar 

  36. Landwehrmeyer GB, et al. Riluzole in Huntington’s disease: a 3-year, randomized controlled study. Ann Neurol. 2007;62(3):262–72.

    Article  CAS  PubMed  Google Scholar 

  37. Huntington Study Group. Dosage effects of riluzole in Huntington’s disease: a multicenter placebo-controlled study. Neurology. 2003;61(11):1551–6.

    Article  Google Scholar 

  38. Armstrong MJ, Miyasaki JM. Evidence-based guideline: pharmacologic treatment of chorea in Huntington disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2012;79(6):597–603.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Delorme C, et al. Deep brain stimulation of the internal pallidum in Huntington’s disease patients: clinical outcome and neuronal firing patterns. J Neurol. 2016;263(2):290–8.

    Article  PubMed  Google Scholar 

  40. • Gonzalez V, 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. Longitudinal case series of bilateral GPi DBS in patients with pharmacologically resistant chorea secondary to HD. Provides information about long-term outcomes of DBS therapy for chorea in HD

    Article  PubMed  Google Scholar 

  41. Kang GA, et al. Long-term follow-up of pallidal deep brain stimulation in two cases of Huntington’s disease. J Neurol Neurosurg Psychiatry. 2011;82(3):272–7.

    Article  PubMed  Google Scholar 

  42. Moro E, et al. Bilateral globus pallidus stimulation for Huntington’s disease. Ann Neurol. 2004;56(2):290–4.

    Article  PubMed  Google Scholar 

  43. Velez-Lago FM, et al. Differential and better response to deep brain stimulation of chorea compared to dystonia in Huntington’s disease. Stereotact Funct Neurosurg. 2013;91(2):129–33.

    Article  PubMed  Google Scholar 

  44. Lopez-Sendon Moreno JL, et al. A 5-year follow-up of deep brain stimulation in Huntington’s disease. Parkinsonism Relat Disord. 2014;20(2):260–1.

    Article  PubMed  Google Scholar 

  45. Spielberger S, et al. Deep brain stimulation in Huntington’s disease: a 4-year follow-up case report. Mov Disord. 2012;27(6):806–7. author reply 807-8

    Article  PubMed  Google Scholar 

  46. Racette BA, Perlmutter JS. Levodopa responsive parkinsonism in an adult with Huntington’s disease. J Neurol Neurosurg Psychiatry. 1998;65(4):577–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Reuter I, et al. Late onset levodopa responsive Huntington’s disease with minimal chorea masquerading as Parkinson plus syndrome. J Neurol Neurosurg Psychiatry. 2000;68(2):238–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jongen PJ, Renier WO, Gabreels FJ. Seven cases of Huntington’s disease in childhood and levodopa induced improvement in the hypokinetic—rigid form. Clin Neurol Neurosurg. 1980;82(4):251–61.

    Article  CAS  PubMed  Google Scholar 

  49. Biolsi B, et al. Long-term follow-up of Huntington disease treated by bilateral deep brain stimulation of the internal globus pallidus. J Neurosurg. 2008;109(1):130–2.

    Article  PubMed  Google Scholar 

  50. Magnet MK, Kapfhammer HP, Bonelli RM. Cabergoline in Huntington’s disease: the first case report. Acta Neurol Scand. 2006;113(5):355–6.

    CAS  PubMed  Google Scholar 

  51. Bonelli RM, et al. Pramipexole ameliorates neurologic and psychiatric symptoms in a Westphal variant of Huntington’s disease. Clin Neuropharmacol. 2002;25(1):58–60.

    Article  PubMed  Google Scholar 

  52. Cislaghi G, et al. Bilateral globus pallidus stimulation in Westphal variant of Huntington disease. Neuromodulation. 2014;17(5):502–5.

    Article  PubMed  Google Scholar 

  53. Cubo E, et al. Internal globus pallidotomy in dystonia secondary to Huntington’s disease. Mov Disord. 2000;15(6):1248–51.

    Article  CAS  PubMed  Google Scholar 

  54. Saft C, et al. Dose-dependent improvement of myoclonic hyperkinesia due to valproic acid in eight Huntington’s disease patients: a case series. BMC Neurol. 2006;6:11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Thompson PD, et al. Cortical myoclonus in Huntington’s disease. Mov Disord. 1994;9(6):633–41.

    Article  CAS  PubMed  Google Scholar 

  56. Vogel CM, et al. Myoclonus in adult Huntington’s disease. Ann Neurol. 1991;29(2):213–5.

    Article  CAS  PubMed  Google Scholar 

  57. Paulsen JS, Smith MM, Long JD. Cognitive decline in prodromal Huntington disease: implications for clinical trials. J Neurol Neurosurg Psychiatry. 2013;84(11):1233–9.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Paulsen JS, et al. Distinct cognitive profiles of cortical and subcortical dementia in advanced illness. Neurology. 1995;45(5):951–6.

    Article  CAS  PubMed  Google Scholar 

  59. Hoth KF, et al. Patients with Huntington’s disease have impaired awareness of cognitive, emotional, and functional abilities. J Clin Exp Neuropsychol. 2007;9(4):365–76.

    Article  Google Scholar 

  60. de Tommaso M, et al. Two years’ follow-up of rivastigmine treatment in Huntington disease. Clin Neuropharmacol. 2007;30(1):43–6.

    Article  PubMed  CAS  Google Scholar 

  61. Rot U, et al. Rivastigmine in the treatment of Huntington’s disease. Eur J Neurol. 2002;9(6):689–90.

    Article  CAS  PubMed  Google Scholar 

  62. Sesok S, et al. Cognitive function in early clinical phase Huntington disease after rivastigmine treatment. Psychiatr Danub. 2014;26(3):239–48.

    CAS  PubMed  Google Scholar 

  63. Cubo E, et al. Effect of donepezil on motor and cognitive function in Huntington disease. Neurology. 2006;67(7):1268–71.

    Article  CAS  PubMed  Google Scholar 

  64. Ondo WG, Mejia NI, Hunter CB. A pilot study of the clinical efficacy and safety of memantine for Huntington’s disease. Parkinsonism Relat Disord. 2007;13(7):453–4.

    Article  PubMed  Google Scholar 

  65. Beister A, et al. The N-methyl-D-aspartate antagonist memantine retards progression of Huntington’s disease. J Neural Transm Suppl. 2004;68:117–22.

    Article  CAS  Google Scholar 

  66. Paulsen JS, et al. Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry. 2001;71(3):310–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Levy ML, et al. Apathy is not depression. J Neuropsychiatry Clin Neurosci. 1998;10(3):314–9.

    Article  CAS  PubMed  Google Scholar 

  68. Duff K, et al. Psychiatric symptoms in Huntington’s disease before diagnosis: the predict-HD study. Biol Psychiatry. 2007;62(12):1341–6.

    Article  PubMed  Google Scholar 

  69. Nehl C, Paulsen JS. Cognitive and psychiatric aspects of Huntington disease contribute to functional capacity. J Nerv Ment Dis. 2004;192(1):72–4.

    Article  PubMed  Google Scholar 

  70. van Duijn E, et al. Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY). J Neurol Neurosurg Psychiatry. 2014;85(12):1411–8.

    Article  PubMed  Google Scholar 

  71. 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.

    Article  PubMed  Google Scholar 

  72. Moulton CD, Hopkins CW, Bevan-Jones WR. Systematic review of pharmacological treatments for depressive symptoms in Huntington’s disease. Mov Disord. 2014;29(12):1556–61.

    Article  CAS  PubMed  Google Scholar 

  73. Como PG, et al. A controlled trial of fluoxetine in nondepressed patients with Huntington’s disease. Mov Disord. 1997;12(3):397–401.

    Article  CAS  PubMed  Google Scholar 

  74. Beglinger LJ, et al. Results of the citalopram to enhance cognition in Huntington disease trial. Mov Disord. 2014;29(3):401–5.

    Article  CAS  PubMed  Google Scholar 

  75. Holl AK, et al. Combating depression in Huntington’s disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol. 2010;25(1):46–50.

    Article  PubMed  Google Scholar 

  76. Duff K, et al. Risperidone and the treatment of psychiatric, motor, and cognitive symptoms in Huntington’s disease. Ann Clin Psychiatry. 2008;20(1):1–3.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Ciammola A, et al. Aripiprazole in the treatment of Huntington’s disease: a case series. Neuropsychiatr Dis Treat. 2009;5:1–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Sajatovic M, et al. Clozapine treatment of psychiatric symptoms resistant to neuroleptic treatment in patients with Huntington’s chorea. Neurology. 1991;41(1):156.

    Article  CAS  PubMed  Google Scholar 

  79. Johnston TG. Risperidone long-acting injection and Huntington’s disease: case series with significant psychiatric and behavioural symptoms. Int Clin Psychopharmacol. 2011;26(2):114–9.

    Article  PubMed  Google Scholar 

  80. Lewis CF, DeQuardo JR, Tandon R. ECT in genetically confirmed Huntington’s disease. J Neuropsychiatry Clin Neurosci. 1996;8(2):209–10.

    Article  CAS  PubMed  Google Scholar 

  81. Ranen NG, Peyser CE, Folstein SE. ECT as a treatment for depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 1994;6(2):154–9.

    Article  CAS  PubMed  Google Scholar 

  82. Cusin C, et al. Rapid improvement of depression and psychotic symptoms in Huntington’s disease: a retrospective chart review of seven patients treated with electroconvulsive therapy. Gen Hosp Psychiatry. 2013;35(6):678. e3-5

    Article  PubMed  Google Scholar 

  83. Paulsen JS, et al. Depression and stages of Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2005;17(4):496–502.

    Article  PubMed  Google Scholar 

  84. Di Maio L, et al. Suicide risk in Huntington’s disease. J Med Genet. 1993;30(4):293–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Lipe H, Schultz A, Bird TD. Risk factors for suicide in Huntingtons disease: a retrospective case controlled study. Am J Med Genet. 1993;48(4):231–3.

    Article  CAS  PubMed  Google Scholar 

  86. Wetzel HH, et al. Suicidal ideation in Huntington disease: the role of comorbidity. Psychiatry Res. 2011;188(3):372–6.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Krishnamoorthy A, Craufurd D. Treatment of apathy in Huntington’s disease and other movement disorders. Curr Treat Options Neurol. 2011;13(5):508–19.

    Article  PubMed  Google Scholar 

  88. De Marchi N, Daniele F, Ragone MA. Fluoxetine in the treatment of Huntington’s disease. Psychopharmacology. 2001;153(2):264–6.

    Article  CAS  PubMed  Google Scholar 

  89. Patzold T, Brune M. Obsessive compulsive disorder in Huntington disease: a case of isolated obsessions successfully treated with sertraline. Neuropsychiatry Neuropsychol Behav Neurol. 2002;15(3):216–9.

    PubMed  Google Scholar 

  90. Anderson K, et al. An international survey-based algorithm for the pharmacologic treatment of obsessive-compulsive behaviors in Huntington’s disease. PLoS Curr. 2011;3:Rrn1261.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Ranen NG, et al. Sertraline in the treatment of severe aggressiveness in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 1996;8(3):338–40.

    Article  CAS  PubMed  Google Scholar 

  92. Groves M, et al. An international survey-based algorithm for the pharmacologic treatment of irritability in Huntington’s disease. PLoS Curr. 2011;3:Rrn1259.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Madhusoodanan S, Brenner R. Use of risperidone in psychosis associated with Huntington’s disease. Am J Geriatr Psychiatry. 1998;6(4):347–9.

    CAS  PubMed  Google Scholar 

  94. Seitz DP, Millson RC. Quetiapine in the management of psychosis secondary to Huntington’s disease: a case report. Can J Psychiatr. 2004;49(6):413.

    Google Scholar 

  95. Alpay M, Koroshetz WJ. Quetiapine in the treatment of behavioral disturbances in patients with Huntington’s disease. Psychosomatics. 2006;47(1):70–2.

    Article  PubMed  Google Scholar 

  96. Correia K, et al. The genetic modifiers of motor onsetAge (GeM MOA) website: genome-wide association analysis for genetic modifiers of Huntington’s disease. J Huntingtons Dis. 2015;4(3):279–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Genetic Modifiers of Huntington’s Disease Consortium. Identification of genetic factors that modify clinical onset of Huntington’s disease. Cell. 2015;162(3):516–26.

    Article  CAS  Google Scholar 

  98. Godinho BM, et al. Delivering a disease-modifying treatment for Huntington’s disease. Drug Discov Today. 2015;20(1):50–64.

    Article  CAS  PubMed  Google Scholar 

  99. Shannon KM, Fraint A. Therapeutic advances in Huntington’s disease. Mov Disord. 2015;30(11):1539–46.

    Article  PubMed  Google Scholar 

  100. Dayalu P, Albin RL. Huntington disease: pathogenesis and treatment. Neurol Clin. 2015;33(1):101–14.

    Article  PubMed  Google Scholar 

  101. Huntington Study Group. Announcement of CREST-E early study closure. 2014: HuntingtonStudyGroup.org.

  102. Huntington Study Group. Announcement of 2CARE early study closure. 2012: HuntingtonStudyGroup.org.

  103. Huntington Study Group Reach. H.D.I. Safety, tolerability, and efficacy of PBT2 in Huntington’s disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015;14(1):39–47.

    Article  CAS  Google Scholar 

  104. Sussmuth SD, 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Achey M.A.B. Meet the compound: RP103 (cysteamine bitartrate delayed-release). 2015 [cited 2016; Available from: http://huntingtonstudygroup.org/hd-insights/meet-the-compound-rp103-cysteamine-bitartrate-delayed-release/.]

  106. Multicentric Trial of the Treatment of Huntington’s Disease by Cysteamine (RP103). 2013 [cited 2016; Available from: https://clinicaltrials.gov/ct2/show/NCT02101957.]

  107. Corey-Bloom J, et al. Disease modifying potential of glatiramer acetate in Huntington’s disease. J Huntingtons Dis. 2014;3(3):311–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Pasinetti GM, et al. Neuroprotective and metabolic effects of resveratrol: therapeutic implications for Huntington’s disease and other neurodegenerative disorders. Exp Neurol. 2011;232(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  109. Naia L, Rego AC. Sirtuins: double players in Huntington’s disease. Biochim Biophys Acta. 2015;1852(10 Pt A):2183–94.

    Article  CAS  PubMed  Google Scholar 

  110. Kremer B, et al. Influence of lamotrigine on progression of early Huntington disease: a randomized clinical trial. Neurology. 1999;53(5):1000–11.

    Article  CAS  PubMed  Google Scholar 

  111. Huntington Study Group DOMINO Investigators. A futility study of minocycline in Huntington’s disease. Mov Disord. 2010;25(13):2219–24.

    Article  Google Scholar 

  112. Chan JH, Lim S, Wong WS. Antisense oligonucleotides: from design to therapeutic application. Clin Exp Pharmacol Physiol. 2006;33(5–6):533–40.

    Article  CAS  PubMed  Google Scholar 

  113. Kay C, et al. Personalized gene silencing therapeutics for Huntington disease. Clin Genet. 2014;86(1):29–36.

    Article  CAS  PubMed  Google Scholar 

  114. • Skotte NH, et al. Allele-specific suppression of mutant huntingtin using antisense oligonucleotides: providing a therapeutic option for all Huntington disease patients. PLoS One. 2014;9(9):e107434. Article describing development of stable ASOs targeting SNPs found on a majority of mutant alleles to stop production of mhtt

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Gagnon KT, et al. Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat. Biochemistry. 2010;49(47):10166–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Hu J, Matsui M, Corey DR. Allele-selective inhibition of mutant huntingtin by peptide nucleic acid-peptide conjugates, locked nucleic acid, and small interfering RNA. Ann N Y Acad Sci. 2009;1175:24–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Sun X, et al. Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity. Hum Mol Genet. 2014;23(23):6302–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Kordasiewicz HB, et al. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis. Neuron. 2012;74(6):1031–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Carroll JB, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Wild EJ, Tabrizi SJ. Targets for future clinical trials in Huntington’s disease: what’s in the pipeline? Mov Disord. 2014;29(11):1434–45.

    Article  CAS  PubMed  Google Scholar 

  121. Miller TM, et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 2013;12(5):435–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Ionis Pharmaceuticals, Inc. Safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS-HTTRx in patients with early manifest Huntington's disease. Bethesda: National Library of Medicine (US); 2000. https://clinicaltrials.gov/ct2/show/NCT02519036.

  123. • Aronin N, DiFiglia M. Huntingtin-lowering strategies in Huntington’s disease: antisense oligonucleotides, small RNAs, and gene editing. Mov Disord. 2014;29(11):1455–61. Review article describing in greater detail the function and limitations of various genetic approaches at gene silencing for HD

    Article  CAS  PubMed  Google Scholar 

  124. Kumar A, et al. Huntington’s disease: an update of therapeutic strategies. Gene. 2015;556(2):91–7.

    Article  CAS  PubMed  Google Scholar 

  125. Stanek LM, et al. Silencing mutant huntingtin by adeno-associated virus-mediated RNA interference ameliorates disease manifestations in the YAC128 mouse model of Huntington’s disease. Hum Gene Ther. 2014;25(5):461–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Rolle K, et al. Promising human brain tumors therapy with interference RNA intervention (iRNAi). Cancer Biol Ther. 2010;9(5):396–406.

    Article  PubMed  Google Scholar 

  127. Moreno-Montanes J, et al. Phase I clinical trial of SYL040012, a small interfering RNA targeting beta-adrenergic receptor 2, for lowering intraocular pressure. Mol Ther. 2014;22(1):226–32.

    Article  CAS  PubMed  Google Scholar 

  128. Garriga-Canut M, et al. Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 mice. Proc Natl Acad Sci. 2012;109(45):E3136–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University of Michigan, 1324 Taubman Center, SPC 5322, 1500 E. Medical Center Drive, Ann Arbor, 48109-5322, USA

    Kara J. Wyant, Andrew J. Ridder & Praveen Dayalu

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  1. Kara J. Wyant
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  3. Praveen Dayalu
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Correspondence to Kara J. Wyant.

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Andrew J. Ridder declares no conflict of interest.

Kara J. Wyant has received an educational grant supplying travel and lodging from Medtronic.

Praveen Dayalu is a member and site investigator for the Huntington Study Group (HSG).

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Movement Disorders

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Wyant, K.J., Ridder, A.J. & Dayalu, P. Huntington’s Disease—Update on Treatments. Curr Neurol Neurosci Rep 17, 33 (2017). https://doi.org/10.1007/s11910-017-0739-9

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  • DOI: https://doi.org/10.1007/s11910-017-0739-9

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