Hostname: page-component-745bb68f8f-f46jp Total loading time: 0 Render date: 2025-01-15T12:01:46.323Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical and Research Advances in Huntington's Disease

Published online by Cambridge University Press:  02 December 2014

M. SuttonBrown  and
O. Suchowersky
M. SuttonBrown
Affiliation:
Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
O. Suchowersky
Affiliation:
Departments of Clinical Neurosciences, and Medical Genetics, University of Calgary, Calgary, AB, Canada
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by abnormalities of movement and dementia. No curative treatment is available and HD results in gradually increasing disability. Characterization of the genetic abnormality has dramatically increased our understanding of the underlying mechanisms of the disease process, and has resulted in the development of a number of genetic models. These research tools are forming the basis of advanced work into the diagnosis, pathophysiology, and potential treatment of the disease. Clinically, the availability of genetic testing has eased confirmation of diagnosis in symptomatic individuals. Presymptomatic testing allows at-risk individuals to make informed choices but requires supportive care from physicians. Current clinical treatment is focused on symptom control. Advances in research have resulted in the development of potential neuroprotective strategies which are undergoing clinical testing.

Résumé

RÉSUMÉ

La maladie de Huntington (MH) est une maladie neurodénétrice dominante autosomique caractésépar des mouvements anormaux et une dénce. Il n’existe aucun traitement curatif de cette maladie qui conduit àne invaliditérogressive. La caractésation de l’anomalie gétique a accru significativement notre comprénsion des ménismes sous-jacents et a menéu déloppement de modès gétiques. Ces outils de recherche constituent la base du travail actuel sur le diagnostic, la physiopathologie et les avenues de traitement de la maladie. Au point de vue clinique, la disponibilitéu test gétique a facilitéa confirmation du diagnostic chez les individus symptomatiques. Le test prémptomatique permet aux individus àisque de faire des choix éairémais demande du soutien de la part des mécins. Le traitement actuel de la maladie vise le contrôdes symptô. Les progrède la recherche ont permis de délopper des stratées neuroprotectrices potentielles qui font préntement l’objet d’essais thépeutiques.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 30 , supplement S1: A Peer-Reviewed Supplement to the Canadian Journal of Neurological Sciences , February 2003 , pp. S45 - S52
Copyright
Copyright © The Canadian Journal of Neurological 2003

References

1. Harper, PS. Huntington’s Disease. London: WB Saunders Co. Ltd., 1991: 1–15.Google Scholar
2. Huntington, G. On chorea. Med Surg Reports 1872; 26: 320–321.Google Scholar
3. Folstein, SE, Chase, GA, Wahl, WE, et al. Huntington’s disease in Maryland: clinical aspects of racial variation. Am J Hum Genet 1987; 41: 168–179.Google Scholar
4. Vessie, PR. On the transmission of Huntington chorea for 300 years: the Bures family group. J Nerv Ment Dis 1932; 76: 553.Google Scholar
5. Sanberg, PR, Fibiger, MC, Mark, RF. Body weight and dietary factors in Huntington’s disease patients compared with matched controls. Med J Australia 1981; 1: 407–409.Google Scholar
6. Lodi, R, Schapira, AH, Manners, D, et al. Abnormal in vivo skeletal muscle energy metabolism in Huntington’s disease and dentatorubropallidoluysian atrophy. Ann Neurol 2000; 48: 72–76.Google Scholar
7. Kirkwood, SC, Su, JL, Conneally, PM, Foroud, T. Progression of symptoms in the early and middle stages of Huntington’s disease. Arch Neurol 2001; 58: 273–278.CrossRefGoogle Scholar
8. Snowden, J, Craufurd, D, Griffiths, H, Thompson, J, Neary, D. Longitudinal evaluation of cognitive disorder in Huntington’s disease. J Int Neuropsychol Soc 2001; 7: 33–44.CrossRefGoogle ScholarPubMed
9. Reuter, I, Hu, MTM, Andrew, TC, et al. Late onset levodopa responsive Huntington’s disease with minimal chorea masquerading as Parkinson plus syndrome. J Neurol Neurosurg Psychiatry 2000; 68: 238–241.Google Scholar
10. Gomez-Tortosa, E, MacDonald, ME, Friend, JC, et al. Quantitative neuropathological changes in presymptomatic Huntington’s disease. Ann Neurol 2001; 49: 29–34.Google Scholar
11. Aylward, EH, Codori, AM, Rosenblatt, A, et al. Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington’s disease. Mov Disord 2000; 15: 552–560.Google Scholar
12. Young, AB, Penney, JB, Staroster-Rubinstein, S, et al. PET Scan investigations of Huntington’s disease: cerebral metabolic correlates of neurological features and functional decline. Ann Neurol 1986; 20: 296–303.Google Scholar
13. Reynolds, NC Jr, Hellman, RS, Tikofsky, RS, et al. Single photon emission computerized tomography (SPECT) in detecting neurodegeneration in Huntington’s disease. Nucl Med Commun 2002; 23:13–18.Google Scholar
14. Feigin, A, Leenders, KL, Moeller, JR, et al. Metabolic network abnormalities in early Huntington’s disease: an [(18)F]FDG PET study. J Nucl Med 2001; 42: 1591–1595.Google Scholar
15. Clark, VP, Lai, S, Deckel, AW. Altered functional MRI responses in Huntington’s disease. Neuroreport 2002; 13:703–705.Google Scholar
16. The Huntington’s Disease Collaborative Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 1993; 72: 971–983.Google Scholar
17. Strong, TV, Tagle, DA, Valdes, JM, et al. Widespread expression of the human and rat Huntington’s disease gene in brain and nonneural tissues. Nat Genet 1993; 5: 259–265.Google Scholar
18. Duyao, M, Ambrose, C, Myers, R, et al. Trinucleotide repeat length instability and age of onset in Huntington’s disease. Nat Genet 1993; 4: 387–392.Google Scholar
19. Furtado, S, Suchowersky, O, Rewcastle, NB, et al. The relationship of the trinucleotide repeat sequences and neuropathological changes in Huntington’s disease. Ann Neurol 1996; 39: 132–136.Google Scholar
20. Zuhlke, C, Riess, O, Bockel, B, Lange, H, Thies, U. Mitotic stability and meiotic variability of the (CAG) n repeat in the Huntington disease gene. Hum Mol Genet 1993; 2: 2063–2067.Google Scholar
21. Wexler, NS, Young, AB, Tanzi, RE, et al. Homozygotes for Huntington’s disease. Nature 1987; 326: 194–197.Google Scholar
22. Myers, RM, MacDonald, ME, Koroschetz, WJ, et al. Denovo expansion of a (CAG)n repeat in sporadic Huntington’s disease. Nat Genet 1993; 5: 168–173.Google Scholar
23. Margolis, RL, O’Hearn, E, Rosenblatt, A, et al. A disorder similar to Huntington’s disease is associated with a novel CAG repeat expansion. Ann Neurol 2001; 50: 373–380.Google Scholar
24. Xiang, F, Almquist, EW, Huq, M, et al. A Huntington disease-like neurodegenerative disorder maps to Chromosome 20p. Am J Hum Genet 1998; 63: 1431–1438.Google Scholar
25. Kambouris, M, Bohlega, S, Al-Tahan, A, Meyer, BF. Localization of the gene for a novel autosomal recessive neurodegenerative Huntington-like disorder to 4p15.3. Am J Hum Genet 2000; 66:445–452.Google Scholar
26. Richfield, EK, Vonsattel, JP, MacDonald, ME, et al. Selective loss of striatal preprotachykinin neurons in a phenocopy of Huntington’s disease. Mov Disord 2002; 17:327–332.Google Scholar
27. Margolis, RL, O’Hearn, E, Rosenblatt, A, et al. A disorder similar to Huntington’s disease is associated with a novel CAG repeat expansion. Ann Neurol 2001; 50: 373–380.Google Scholar
28. Stevanin, G, Camuzat, A, Holmes, SE, et al. CAG/CTG repeat expansions at the Huntington’s disease-like 2 locus are rare in Huntington’s disease patients. Neurol 2002; 58: 965–967.CrossRefGoogle ScholarPubMed
29. Mangiarini, L, Sathasivam, K, Seller, M, et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 1996; 87: 493–506.Google Scholar
30. Schilling, G, Becher, MW, Sharp, AH, et al. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 1999; 8: 397–407.Google Scholar
31. Reddy, PH, Williams, M, Charles, V, et al. Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat Genet 1998; 20: 198–202.Google Scholar
32. Hodgson, J, Agopyan, N, Gutekunst, C-A, et al. AYAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 1999; 23: 181–192.Google Scholar
33. White, JK, Auerbach, W, Duyao, MP, et al. Huntingtin is required for neurogenesis and is not impaired by the Huntington’s disease CAG expansion. Nat Genet 1997; 17: 404–410.Google Scholar
34. Shelbourne, PF, Killeen, N, Hevner, RF, et al. A Huntington’s disease CAG expansion at the murine Hdh locus is unstable and associated with behavioral abnormalities in mice. Hum Mol Genet 1999; 8: 763–774.Google Scholar
35. Wheeler, VC, Auerbach, W, White, JK, et al. Length-dependent gametic CAG repeat instability in the Huntington’s disease knock-in mouse. Hum Mol Genet 1999; 8: 115–122.Google Scholar
36. Wheeler, VC, White, JK, Gutekunst, C-A, et al. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knockin mice. Hum Mol Genet 2000; 9: 503–513.Google Scholar
37. Lione, LA, Carter, RJ, Hunt, MJ, et al. Selective discrimination learning impairments in mice expressing the human Huntington’s disease mutation. J Neurosci 1999; 19: 10428–10437.Google Scholar
38. Carter, RJ, Lione, LA, Humby, T, et al. Characterization of progressive motor deficits in mice transgenic for the human Huntington’s disease mutation. J Neurosci 1999; 19: 3248–3257.Google Scholar
39. Jackson, GR, Salecker, I, Dong, X, et al. Polyglutamine-expanded human huntingtin transgenes induced degeneration of Drosophila photoreceptor neurons. Neuron 1998; 21: 633–642.Google Scholar
40. Faber, PW, Alter, JR, MacDonald, ME, Hart, AC. Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron. Proc Natl Acad Sci USA 1999; 96: 179–184.Google Scholar
41. Almqvist, EW, Bloch, M, et al. A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease. Am J Hum Genet 1999; 64: 1293–1304.Google Scholar
42. Simpson, SA, Harper, PS. Prenatal testing for Huntington’s disease: experience within the UK 1994–1998. J Med Genet 2001; 38: 333–335.Google Scholar
43. Vonsattel, JM, Myers, RH, Stevens, TJ, et al. Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol 1985;44:559–577.Google Scholar
44. Rodda, RA. Cerebellar atrophy in Huntington’s disease. J Neurol Sci 1981; 50: 147–157.Google Scholar
45. Hedreen, JC, Peyser, CE, Folstein, SE, Ross, CA. Neuronal loss in layers V and VI of cerebral cortex in Huntington’s disease. Neurosci Lett 1991; 133: 257–261.Google Scholar
46. Jackson, M, Gentleman, S, Lennox, G, et al. The cortical neuritic pathology of Huntington’s disease. Neuropathol Appl Neurobiol 1995; 21: 18–26.Google Scholar
47. Difiglia, M. Excitotoxic injury of the neostriatum is a model for Huntington’s disease. Trends Neurosci 1990; 13: 286–289.Google Scholar
48. McGeer, EG, McGeer, PL. Duplication of biochemical changes of Huntington’s chorea by intrastriatal injections of glutamic acid and kainic acid. Nature 1976; 263: 517–519.Google Scholar
49. Beal, MF, Kowall, NW, Ellison, DW, et al. Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid. Nature 1986; 321: 163–171.Google Scholar
50. Coyle, JT, Puttfarcken, P. Oxidative stress, glutamate and neurodegenerative disorders. Science 1993; 262: 689–695.Google Scholar
51. Wolfensberger, M, Amsler, V, Cuenod, M, et al. Identification of quinolinic acid in rat and human brain tissue. Neurosci Lett 1983; 41: 247–252.Google Scholar
52. Nicholson, LF, Faull, RL, Waldvogel, HJ, Dragunow, M. GABAand GABA A receptor changes in the substantia nigra of the rat following quinolinic acid lesions in the striatum closely resemble Huntington’s disease. Neuroscience 1995; 66: 507–521.Google Scholar
53. Ferrante, RJ, Kowall, NW, Cipolloni, PB, Storey, E, Beal, MF. Excitotoxin lesions in primates as a model for Huntington’s disease: histopathologic and neurochemical characterization. Exp Neurol 1993; 119: 46–71.Google Scholar
54. Guidetti, P, Charles, V, Chen, E, et al. Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energ y production. Exp Neurol 2001; 169: 340–350.CrossRefGoogle Scholar
55. Metzler, M, Chen, N, Helgason, CD, et al. Life without huntingtin: normal differentiation into functional neurons. Neurochemistry 1999; 72: 1009–1018.Google Scholar
56. Hilditch-Maguire, P, Trettel, F, Passani, LA, et al. Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organelles. Hum Mol Genet 2000; 9: 2789–2797.Google Scholar
57. Iannicola, C, Moreno, S, Oliverio, S, et al. Early alterations in gene expression and cell morphology in a mouse model of Huntington’s Disease. J Neurochem 2000; 75: 830–839.Google Scholar
58. Cha, JH, Kosinski, CM, Kerner, JA, et al. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci USA. 1998; 95:6480–6485.Google Scholar
59. Saudou, F, Finkbeiner, S, Devys, D, Greenberg, ME. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with formation of intranuclear inclusions. Cell 1998; 95: 55–66.Google Scholar
60. Zuccato, C, Ciammola, A, Rigamonti, D, et al. Loss of Huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science 2001; 293: 493–498.Google Scholar
61. Dunah, AW, Jeong, H, Griffin, A, et al. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington’s disease. Science 2002; 296:2238–2243.Google Scholar
62. Davies, SW, Turmaine, M, Cozens, BA, et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997; 90: 537–548.Google Scholar
63. Difiglia, M, Sapp, E, Chase, KO, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997; 277: 1990–1993.Google Scholar
64. Ferrigno, P, Silver, PA. Polyglutamine expansions: proteolysis, chaperones, and the dangers of promiscuity. Neuron 2000; 26: 912.Google Scholar
65. Roizin, L, Stellar, S, Liu, JC. Neuronal nuclear-cytoplasmic changes in Huntington’s chorea: electron microscope investigations. Adv Neurol 1979; 23: 95–122.Google Scholar
66. Roos, RAC, Bots, GTAM. Nuclear membrane indentations in Huntington’s chorea. J Neurol Sci 1983; 61: 37–47.CrossRefGoogle ScholarPubMed
67. Ordway, JM, Tallaksen-Greene, S, Gutekunst, CA, et al. Ectopically expressed CAG repeats caused intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell 1997; 91: 753–763.Google Scholar
68. Kuemmerle, S, Gutekunst, CA, Klein, AM, et al. Huntingtin aggregates may not predict neuronal death in Huntington’s disease. Ann Neurol 1999; 46: 842–849.Google Scholar
69. Gutekunst, CA, Li, SH, Yi, H, et al. Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology. J Neurosci 1999; 19: 2522–2534.Google Scholar
70. Kim, M, Lee, H-S, LaForet, G, et al. Mutant huntingtin expression in clonal striatal cells: dissociation of inclusion formation and neuronal survival by caspase inhibition. J Neurosci 1999; 19: 964–973.Google Scholar
71. Cooper, JK, Schilling, G, Peters, MF, et al. Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum Mol Genet 1998; 7: 783–790.Google Scholar
72. Hackam, A, Singaraja, T, Wellington, CL, et al. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J Cell Biol 1998; 141: 1097–1105.Google Scholar
73. Wellington, CL, Ellerby, LM, Hackam, AS, et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem 1998; 273: 9158–9167.Google Scholar
74. Hodgson, JG, Agopyan, N, Gutekunst, C-A, et al. A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 1999; 23:181–192.Google Scholar
75. Li, H, Li, SH, Cheng, AL, et al. Ultrastructural localization and progressive formation of neuropil aggregates in Huntington’s disease transgenic mice. Hum Mol Gen 1999; 8:1227–1236.CrossRefGoogle ScholarPubMed
76. Wellington, CL, Hayden, MR. Of molecular interactions, mice and mechanisms: new insights into Huntington’s disease. Curr Opin Neurol 1997; 10: 291–298.Google Scholar
77. Wellington, CL, Ellerby, LM, Hackam, AS, et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem 1998; 273: 9158–9167.Google Scholar
78. Nuñez, G, Benedict, MA, Hu, Y, Inohara, N. Caspases: the proteases of the apoptotic pathway. Oncogene 1998; 17: 3237–3245.Google Scholar
79. Wellington, CL, Hayden, MR. Caspases and neurodegeneration: on the cutting edge of new therapeutic approaches. Clin Genet 2000; 57: 1–10.Google Scholar
80. Wellington, CL, Singaraja, R, Ellerby, L, et al. Inhibition of caspase cleavage of huntingtin protects neurons from toxicity and aggregate formation. Am J Hum Genet 1999; 65: A4.Google Scholar
81. Trottier, Y, Lutz, Y, Stevanin, G, et al. Polyglutamate expansion as a pathological epitope in Huntington’s disease and four dominant cerebellar ataxias. Nature 1995; 378:403–406.Google Scholar
82. Rigamonti, D, Bauer, JH, De-Fraja, C, et al. Wild-type huntingtin protects from apoptosis upstream of caspase-3. J Neurosci 2000; 20: 3705–3713.Google Scholar
83. Leavitt, BR, Guttman, JA, Hodgson JG, et al. Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo. Am J Hum Genet 2001; 68: 313–324.Google Scholar
84. Hackam, AS, Yassa, AS, Singaraja, R. Huntingtin Interacting Protein 1 induces apoptosis via a novel caspase-dependent death effector domain. J Biol Chem 2000; 275: 41299–41308.CrossRefGoogle Scholar
85. Brouillet, E, Conde, F, Beal, MF, Hantraye, P. Replicating Huntington’s disease phenotype in experimental animals. Prog Neurobiol 1999; 59: 427–468.Google Scholar
86. Beal, MF. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann Neurol 1992; 31: 119–130.Google Scholar
87. Coles, CJ, Edmonson, DE, Singer, TP. Inactivation of succinate dehydrogenase by 3-nitropropionate. J Biol Chem 1979; 255: 4772–4780.Google Scholar
88. Peraica, M, Radic, B, Lucic, A, Pavlovic, M. Toxic effects of mycotoxins in humans. Bull World Health Org 1999; 77: 754–766.Google Scholar
89. Beal, MF, Brouillet, FE, Jenkins, BG, et al. Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 1993; 13: 4186–4192.Google Scholar
90. Borlongan, CV, Koutouzis, TK, Freeman, TB, Cahill, DW, Sanberg, PR. Behavioral pathology induced by repeated systemic injections of 3-nitropropionic acid mimics the motor symptoms of Huntington’s disease. Brain Res 1995; 697: 254–257.Google Scholar
91. Gu, M, Gash, MT, Mann, VM, et al. Mitochondrial defect in Huntington’s disease caudate nucleus. Ann Neurol 1996; 39: 385–389.Google Scholar
92. Ellison, DW, Beal, MF, Mazurek, MF, et al. Amino acid neurotransmitter abnormalities in Huntington’s disease and the quinolinic acid animal model of Huntington’s disease. Brain 1987; 110: 1657–1673.Google Scholar
93. Beal, MF, Henshaw, DR, Jenkins, BG, Rosen, BR, Schulz, JB. Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin Malonate. Ann Neurol 1994; 36: 882–888.Google Scholar
94. Ferrante, RJ, Andreassen, OA, Dedeoglu, A, et al. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington’s disease. J Neurosci 2002; 22:1592–1599.Google Scholar
95. The Huntington Study Group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington’s disease. Neurology 2001; 57: 397–404.Google Scholar
96. Gimenez-Roldan, S, Mateo, D. Huntington disease: tetrabenazine compared to haloperidol in the reduction of involuntary movements. Neurologia 1989; 4: 282–287.Google ScholarPubMed
97. Bogelman, G, Hirschmann, S, Modai, I. Olanzapine and Huntington’s disease. J Clin Psychopharmacol 2001; 21:245–246.Google Scholar
98. Dallocchio, C, Buffa, C, Tinelli, C, Mazzarello, P. Effectiveness of risperidone in Huntington chorea patients. J Clin Psychopharmacol 1999; 19(1):101–103.Google Scholar
99. Parsa, MA, Szigethy, E, Voci, JM, Meltzer, HY. Risperidone in treatment of choreoathetosis of Huntington’s disease. J Clin Psychopharmacol 1997; 17(2):134–135.Google Scholar
100. Metman, LV, Morris, MJ, Farmer, C, et al. Huntington’s disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology 2002; 59: 694–699.Google Scholar
101. Ferrante, RJ, Andreassen, OA, Jenkins, BG, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J Neurosci 2000; 20; 4389–4397.Google Scholar
102. Anderassen, OA, et al. Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington’s disease. Neurobiol Dis 2001; 8: 479–491.Google Scholar
103. Chen, M, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 2000; 6: 797–801.Google Scholar
104. Kremer, B, Clark, CM, Almqvist, EW, et al. Influence of lamotrigine on progression of early Huntington’s disease: a randomized clinical trial. Neurology 1999; 53: 1000–1011 Google Scholar
105. Palfi, S, Conde, F, Riche, D, et al. Fetal striatal allografts reverse cognitive deficits in a primate model of Huntington disease. Nat Med 1998; 4:727–729.Google Scholar
106. Hauser, RA, Furtado, S, Cimino, CR, et al. Bilateral human fetal striatal transplantation in Huntington’s disease. Neurology 2002; 58: 687–695.Google Scholar
107. Bachoud-Lefi, AC, Remy, P, Nguyen, JP, et al. Motor and cognitive improvements in patients with Huntington’s disease after neural transplantation. Lancet 2000; 356: 1975–1979.Google Scholar
108. Bonelli, RM, Gruber, A. Deep brain stimulation in Huntington’s disease. Mov Disord 2002;17: 429–430.Google Scholar
109. Joel, D. Open interconnected model of basal ganglia-thalamo-cortical circuitry and it’s relevance to the clinical syndrome of Huntington’s disease. Mov Disord 2001; 16: 407–423.Google Scholar
110. Yamamoto, A, Lucas, JJ, Hen, R. Reversal of a neuropathology and motor dysfunction in a conditional model of Huntington’s disease. Cell 2000; 101: 57–66.Google Scholar