Machado Joseph disease: Clinical and genetic aspects, and current treatment

Expert Opinion on Orphan Drugs

Volumn 3, Issue 5, 2015, Pages 517-535

  Saute, Jonas Alex Morales ^a   Jardim, Laura Bannach ^a,b,c  

^a HOSPITAL DE CLÍNICAS DE PORTO ALEGRE   (Brazil)

^b FEDERAL UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^c Instituto Nacional de Genética Médica Populacional INAGEMP   (Brazil)

Author keywords

Ataxin 3; Disease modifying treatment; Machado Joseph disease; Polyglutamine disorders; Pre implantation diagnosis; Spinocerebellar ataxia type 3; Symptomatic treatment

Indexed keywords

ANTIDEPRESSANT AGENT; ATAXIN 3; BENSERAZIDE; BENZODIAZEPINE DERIVATIVE; BOTULINUM TOXIN; CARBAMAZEPINE; CARBIDOPA PLUS LEVODOPA; CHOLINERGIC RECEPTOR BLOCKING AGENT; FAMPRIDINE; LEVODOPA; LITHIUM CARBONATE; MELATONIN; MEXILETINE; NONSTEROID ANTIINFLAMMATORY AGENT; OPIATE; RILUZOLE; VARENICLINE;

ATAXIA; CAG REPEAT; CLINICAL FEATURE; CLINICAL TRIAL (TOPIC); DISEASE COURSE; DYSARTHRIA; DYSPHAGIA; DYSTONIA; EYE MOVEMENT DISORDER; FATIGUE; GENETIC COUNSELING; GENETIC SCREENING; GENETIC TRAIT; HETEROZYGOSITY; HOMOZYGOSITY; HUMAN; MACHADO JOSEPH DISEASE; MEDICAL HISTORY; MEIOTIC RECOMBINATION; MENTAL DISEASE; MITOTIC RECOMBINATION; MOLECULAR PATHOLOGY; MUSCLE CRAMP; NEUROPATHOLOGY; NONHUMAN; PAIN; PALLIATIVE THERAPY; PARKINSONISM; PATHOGENESIS; PHASE 3 CLINICAL TRIAL (TOPIC); PHYSIOTHERAPY; PLEIOTROPY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SLEEP DISORDER; SPASTICITY; STEM CELL TRANSPLANTATION; SYSTEMATIC REVIEW (TOPIC);

EID: 84928636939     PISSN: None     EISSN: 21678707     Source Type: Journal    
DOI: 10.1517/21678707.2015.1025747     Document Type: Review

References (141)

1. Nakano KK, Dawson DM, Spence A. Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts. Neurology 1972;22:49-55
2. Woods BT, Schaumburg HH. Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia. A unique and partially treatable clinico-pathological entity. J Neurol Sci 1972;17:149-66
3. Rosenberg RN, Nyhan WL, Bay C, Shore P. Autosomal dominant striatonigral degeneration. A clinical, pathologic, and biochemical study of a new genetic disorder. Neurology 1976;26:703-14
4. Takiyama Y, Nishizawa M, Tanaka H, et al. The gene for Machado-Joseph disease maps to human chromosome 14q. Nat Genet 1993;4:300-4
5. Kawaguchi Y, Okamoto T, Taniwaki M, et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 1994;8:221-8
6. Sequeiros J, Martins S, Silveira I. Epidemiology and population genetics of degenerative ataxias. Handb Clin Neurol 2012;103:227-51
7. de Castilhos RM, Furtado GV, Gheno TC, et al. Spinocerebellar ataxias in Brazil - frequencies and modulating effects of related genes. Cerebellum 2014;13:17-28
8. Coutinho P, Ruano L, Loureiro JL, et al. Hereditary ataxia and spastic paraplegia in Portugal: a population-based prevalence study. JAMA Neurol 2013;70:746-55
9. Prestes PR, Saraiva-Pereira ML, Silveira I, et al. Machado-Joseph disease enhances genetic fitness: a comparison between affected and unaffected women and between MJD and the general population. Ann Hum Genet 2008;72:57-64
10. Martins S, Soong B-W, Wong VCN, et al. Mutational origin of Machado-Joseph disease in the Australian Aboriginal communities of Groote Eylandt and Yirrkala. Arch Neurol 2012;69:746-51
11. Costa M do C, Paulson HL. Toward understanding Machado-Joseph disease. Prog Neurobiol 2012;97:239-57
12. Schmitt I, Linden M, Khazneh H, et al. Inactivation of the mouse Atxn3 (ataxin-3) gene increases protein ubiquitination. Biochem Biophys Res Commun 2007;362:734-9
13. Alves S, Nascimento-Ferreira I, et al. Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3? Hum Mol Genet 2010;19:2380-94
14. Sobue G, Doyu M, Nakao N, et al. Homozygosity for Machado-Joseph disease gene enhances phenotypic severity. J Neurol Neurosurg Psychiatry 1996;60:354-6
15. Lerer I, Merims D, Abeliovich D, et al. Machado-Joseph disease: correlation between the clinical features, the CAG repeat length and homozygosity for the mutation. Eur J Hum Genet 1996;4:3-7
16. Fukutake T, Shinotoh H, Nishino H, et al. Homozygous Machado-Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms. Eur J Neurol 2002;9:97-100
17. Gordon CR, Joffe V, Vainstein G, Gadoth N. Vestibulo-ocular arreflexia in families with spinocerebellar ataxia type 3 (Machado-Joseph disease). J Neurol Neurosurg Psychiatry 2003;74:1403-6
18. Lysenko L, Grewal RP, Ma W, Peddareddygari LR. Homozygous Machado Joseph Disease: a case report and review of literature. Can J Neurol Sci 2010;37:521-3
19. Maciel P, Costa MC, Ferro A, et al. Improvement in the molecular diagnosis of Machado-Joseph disease. Arch Neurol 2001;58:1821-7
20. Carvalho DR, La Rocque-Ferreira A, Rizzo IM, et al. Homozygosity enhances severity in spinocerebellar ataxia type 3. Pediatr Neurol 2008;38:296-9
21. Jardim LB, Pereira ML, Silveira I, et al. Machado-Joseph disease in South Brazil: clinical and molecular characterization of kindreds. Acta Neurol Scand 2001;104:224-31
22. Sasaki H, Wakisaka A, Fukazawa T, et al. CAG repeat expansion of Machado-Joseph disease in the Japanese: analysis of the repeat instability for parental transmission, and correlation with disease phenotype. J Neurol Sci 1995;133:128-33
23. Dürr A, Stevanin G, Cancel G, et al. Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. Ann Neurol 1996;39:490-9
24. Gu W, Ma H, Wang K, et al. The shortest expanded allele of the MJD1 gene in a Chinese MJD kindred with autonomic dysfunction. Eur Neurol 2004;52:107-11
25. Martins S, Coutinho P, Silveira I, et al. Cis-acting factors promoting the CAG intergenerational instability in Machado-Joseph disease. Am J Med Genet B Neuropsychiatr Genet 2008;147:439-46
26. Lopes-Cendes I, Maciel P, et al. Somatic mosaicism in the central nervous system in spinocerebellar ataxia type 1 and Machado-Joseph disease. Ann Neurol 1996;40:199-206
27. Maciel P, Gaspar C, DeStefano AL, et al. Correlation between CAG repeat length and clinical features in Machado-Joseph disease. Am J Hum Genet 1995;57:54-61
28. Iughetti P, Otto PA, Zatz M, et al. Different behavior in the paternally vs. maternally inherited mutated allele in Brazilian Machado-Joseph (MJD1) families. Am J Med Genet 1998;77:246-8
29. Takiyama Y, Sakoe K, Soutome M, et al. Single sperm analysis of the CAG repeats in the gene for Machado-Joseph disease (MJD1): evidence for non-Mendelian transmission of the MJD1 gene and for the effect of the intragenic CGG/GGG polymorphism on the intergenerational instability. Hum Mol Genet 1997;6:1063-8
30. Frontali M, Sabbadini G, Novelletto A, et al. Genetic fitness in Huntington?s Disease and Spinocerebellar Ataxia 1: a population genetics model for CAG repeat expansions. Ann Hum Genet 1996;60:423-35
31. Jardim LB, Pereira ML, Silveira I, et al. Neurologic findings in Machado-Joseph disease: relation with disease duration, subtypes, and (CAG)n. Arch Neurol 2001;58:899-904
32. França MC, D?Abreu A, Nucci A, et al. Progression of ataxia in patients with Machado-Joseph disease. Mov Disord 2009;24:1387-90
33. Jardim LB, Hauser L, Kieling C, et al. Progression rate of neurological deficits in a 10-year cohort of SCA3 patients. Cerebellum 2010;9:419-28
34. Jacobi H, Bauer P, Giunti P, et al. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology 2011;77:1035-41
35. Reetz K, Costa AS, Mirzazade S, et al. Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6. Brain 2013;136:905-17
36. Kieling C, Prestes PR, Saraiva-Pereira ML, Jardim LB. Survival estimates for patients with Machado-Joseph disease (SCA3). Clin Genet 2007;72:543-5
37. Rüb U, Schöls L, Paulson H, et al. Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7. Prog Neurobiol 2013;104:38-66
38. Coutinho P, Andrade C. Autosomal dominant system degeneration in Portuguese families of the Azores Islands. A new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology 1978;28:703-9
39. Schmitz-Hübsch T, Coudert M, Bauer P, et al. Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms. Neurology 2008;71:982-9
40. Trouillas P, Takayanagi T, Hallett M, et al. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci 1997;145:205-11
41. Schmitz-Hübsch T, Fimmers R, Rakowicz M, et al. Responsiveness of different rating instruments in spinocerebellar ataxia patients. Neurology 2010;74:678-84
42. Kieling C, Rieder CRM, Silva ACF, et al. A neurological examination score for the assessment of spinocerebellar ataxia 3 (SCA3). Eur J Neurol 2008;15:371-6
43. Camey S, Jardim LB, Kieling C, et al. A prospective study of SCA3 gait ataxia described through a Markovian method. Neuroepidemiology 2010;34:163-70
44. Jacobi H, Reetz K, du Montcel ST, et al. Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3 and 6 in the longitudinal RISCA study: analysis of baseline data. Lancet Neurol 2013;12:650-8
45. Saute JA, Donis KC, Serrano-Munuera C, et al. Ataxia rating scales-psychometric profiles, natural history and their application in clinical trials. Cerebellum 2012;11:488-504
46. Jardim L, Silveira I, Pereira ML, et al. Searching for modulating effects of SCA2, SCA6 and DRPLA CAG tracts on the Machado-Joseph disease (SCA3) phenotype. Acta Neurol Scand 2003;107:211-14
47. Tezenas du Montcel S, Durr A, Bauer P, et al. Modulation of the age at onset in spinocerebellar ataxia by CAG tracts in various genes. Brain 2014;137:2444-55
48. Bettencourt C, Raposo M, Kazachkova N, et al. The APOE epsilon2 allele increases the risk of earlier age at onset in Machado-Joseph disease. Arch Neurol 2011;68:1580-3
49. Siebert M, Donis KC, Socal M, et al. Glucocerebrosidase gene variants in parkinsonian patients with Machado Joseph/spinocerebellar ataxia 3. Parkinsonism Relat Disord 2012;18:185-90
50. Emmel VE, Alonso I, Jardim LB, et al. Does DNA methylation in the promoter region of the ATXN3 gene modify age at onset in MJD (SCA3) patients? Clin Genet 2011;79:100-2
51. Schmitz-Hübsch T, Coudert M, Tezenas du Montcel S, et al. Depression comorbidity in spinocerebellar ataxia. Mov Disord 2011;26:870-6
52. Pedroso JL, França MC, Braga-Neto P, et al. Nonmotor and extracerebellar features in Machado-Joseph disease: a review. Mov Disord 2013;28:1200-8
53. Paulson HL, Das SS, Crino PB, et al. Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain. Ann Neurol 1997;41:453-62
54. Schmidt T, Landwehrmeyer GB, Schmitt I, et al. An isoform of ataxin-3 accumulates in the nucleus of neuronal cells in affected brain regions of SCA3 patients. Brain Pathol 1998;8(4):669-79
55. Rüb U, Brunt ER, Deller T. New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado-Joseph disease). Curr Opin Neurol 2008;21:111-16
56. Seidel K, den Dunnen WFA, Schultz C, et al. Axonal inclusions in spinocerebellar ataxia type 3. Acta Neuropathol 2010;120:449-60
57. Seidel K, Meister M, Dugbartey GJ, et al. Cellular protein quality control and the evolution of aggregates in spinocerebellar ataxia type 3 (SCA3). Neuropathol Appl Neurobiol 2012;38:548-58
58. Cummings CJ, Reinstein E, Sun Y, et al. Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice. Neuron 1999;24:879-92
59. Nagai Y, Inui T, Popiel HA, et al. A toxic monomeric conformer of the polyglutamine protein. Nat Struct Mol Biol 2007;14:332-40
60. Bichelmeier U, Schmidt T, Hübener J, et al. Nuclear localization of ataxin-3 is required for the manifestation of symptoms in SCA3: in vivo evidence. J Neurosci 2007;27:7418-28
61. Chou A-H, Yeh T-H, Ouyang P, et al. Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice by inducing transcriptional dysregulation. Neurobiol Dis 2008;31:89-101
62. Sequeiros J, Seneca S, Martindale J. Consensus and controversies in best practices for molecular genetic testing of spinocerebellar ataxias. Eur J Hum Genet 2010;18:1188-95
63. Van de Warrenburg BPC, van Gaalen J, Boesch S, et al. EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. Eur J Neurol 2014;21:552-62
64. Wertz DC, Fletcher GF, Berg K. Programme WHG. Review of ethical issues in medical genetics: report of consultants to WHO. World Health Organization. 2003
65. Schuler-Faccini L, Osorio CM, Romariz F, et al. Genetic counseling and presymptomatic testing programs for Machado-Joseph disease: lessons from Brazil and Portugal. Genet Mol Biol 2014;37:263-70
66. Colomer Gould VF. Mouse models of spinocerebellar ataxia type 3 (Machado-Joseph disease). Neurotherapeutics 2012;9(2):285-96
67. Correia M, Coutinho P, Silva MC, et al. Evaluation of the effect of sulphametoxazole and trimethoprim in patients with Machado-Joseph disease. Rev Neurol 1995;23:632-4
68. Sakai T, Matsuishi T, Yamada S, et al. Sulfamethoxazole-trimethoprim doubleblind, placebo-controlled, crossover trial in Machado-Joseph disease: sulfamethoxazole-trimethoprim increases cerebrospinal fluid level of biopterin. J Neural Transm Gen Sect 1995;102:159-72
69. Schulte T, Mattern R, Berger K, et al. Double-blind crossover trial of trimethoprim-sulfamethoxazole in spinocerebellar ataxia type 3/Machado-Joseph disease. Arch Neurol 2001;58:1451-7
70. Wessel K, Langenberger K, Nitschke MF, Kömpf D. Double-blind crossover study with physostigmine in patients with degenerative cerebellar diseases. Arch Neurol 1997;54:397-400
71. Monte TL, Rieder CRM, Tort AB, et al. Use of fluoxetine for treatment of Machado-Joseph disease: an open-label study. Acta Neurol Scand 2003;107:207-10
72. Takei A, Hamada S, Homma S, et al. Difference in the effects of tandospirone on ataxia in various types of spinocerebellar degeneration: an openlabel study. Cerebellum 2010;9:567-70
73. Liu C-S, Hsu H-M, Cheng W-L, Hsieh M. Clinical and molecular events in patients with Machado-Joseph disease under lamotrigine therapy. Acta Neurol Scand 2005;111:385-90
74. Assadi M, Campellone JV, Janson CG, et al. Treatment of spinocerebellar ataxia with buspirone. J Neurol Sci 2007;260:143-6
75. Arpa J, Sanz-Gallego I, Medina-Báez J, et al. Subcutaneous insulin-like growth factor-1 treatment in spinocerebellar ataxias: an open label clinical trial. Mov Disord 2011;26:358-9
76. du Montcel ST, Charles P, Ribai P, et al. Composite cerebellar functional severity score: validation of a quantitative score of cerebellar impairment. Brain 2008;131:1352-61
77. Schmitz-Hübsch T, Giunti P, Stephenson DA, et al. SCA Functional Index: a useful compound performance measure for spinocerebellar ataxia. Neurology 2008;71:486-92
78. Giordano I, Bogdanow M, Jacobi H, et al. Experience in a short-term trial with 4-aminopyridine in cerebellar ataxia. J Neurol 2013;260:2175-6
79. Saute JA, de Castilhos RM, Monte TL, et al. A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease. Mov Disord 2014;29:568-73
80. Chan E, Charles P, Ribai P, et al. Quantitative assessment of the evolution of cerebellar signs in spinocerebellar ataxias. Mov Disord 2011;26:534-8
81. Boy J, Schmidt T, Wolburg H, et al. Reversibility of symptoms in a conditional mouse model of spinocerebellar ataxia type 3. Hum Mol Genet 2009;18:4282-95
82. Matilla-Duen?as A, Ashizawa T, Brice A, et al. Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias. Cerebellum 2014;13:269-302
83. Saute JA, da Silva ACF, Muller AP, et al. Serum insulin-like system alterations in patients with spinocerebellar ataxia type 3. Mov Disord 2011;26:731-5
84. Zijlstra MP, Rujano MA, Van Waarde MA, et al. Levels of DNAJB family members (HSP40) correlate with disease onset in patients with spinocerebellar ataxia type 3. Eur J Neurosci 2010;32:760-70
85. Tort ABL, Portela LV, Rockenbach IC, et al. S100B and NSE serum concentrations in Machado Joseph disease. Clin Chim Acta 2005;351:143-8
86. Zhou J, Lei L, Shi Y, et al. Serum concentrations of NSE and S100B in spinocerebellar ataxia type 3/Machado-Joseph disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2011;36:504-10
87. Shi Y, Huang F, Tang B, et al. MicroRNA profiling in the serums of SCA3/MJD patients. Int J Neurosci 2014;124:97-101
88. Adityanjee Munshi KR, Thampy A. The syndrome of irreversible lithiumeffectuated neurotoxicity. Clin Neuropharmacol 2005;28:38-49
89. Sacca F, Puorro G, Brunetti A, et al. A randomized controlled pilot trial of lithium in spinocerebellar ataxia type 2. J Neurol 2015;262(1):149-53
90. Yang W-Z, Zhang Y, Wu F, et al. Human umbilical cord blood-derived mononuclear cell transplantation: case series of 30 subjects with Hereditary Ataxia. J Transl Med 2011;9:65
91. Jin J-L, Liu Z, Lu Z-J, et al. Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia. Curr Neurovasc Res 2013;10:11-20
92. Zesiewicz TA, Greenstein PE, Sullivan KL, et al. A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3. Neurology 2012;78:545-50
93. Connolly BS, Prashanth LK, Shah BB, et al. A randomized trial of varenicline (chantix) for the treatment of spinocerebellar ataxia type 3. Neurology 2012;79:2218
94. Ristori G, Romano S, Visconti A, et al. Riluzole in cerebellar ataxia: a randomized, double-blind, placebocontrolled pilot trial. Neurology 2010;74:839-45
95. Fonteyn EM, Keus SH, Verstappen CC, van de Warrenburg BP. Physiotherapy in degenerative cerebellar ataxias: utilisation, patient satisfaction, and professional expertise. Cerebellum 2013;12:841-7
96. Ilg W, Synofzik M, Brötz D, et al. Intensive coordinative training improves motor performance in degenerative cerebellar disease. Neurology 2009;73:1823-30
97. Fonteyn EM, Heeren A, Engels J, et al. Gait adaptability training improves obstacle avoidance and dynamic stability in patients with cerebellar degeneration. Gait Posture 2014;40:247-51
98. Miyai I, Ito M, Hattori N, et al. Cerebellar ataxia rehabilitation trial in degenerative cerebellar diseases. Neurorehabil Neural Repair 2012;26:515-22
99. Freeman W, Wszolek Z. Botulinum toxin type A for treatment of spasticity in spinocerebellar ataxia type 3 (Machado-Joseph disease). Mov Disord 2005;20:644
100. Cardoso F, de Oliveira JT, Puccioni-Sohler M, et al. Eyelid dystonia in Machado-Joseph disease. Mov Disord 2000;15:1028-30
101. Tuite PJ, Lang AE. Severe and prolonged dysphagia complicating botulinum toxin A injections for dystonia in Machado-Joseph disease. Neurology 1996;46:846
102. Wilder-Smith E, Tan EK, Law HY, et al. Spinocerebellar ataxia type 3 presenting as an L-DOPA responsive dystonia phenotype in a Chinese family. J Neurol Sci 2003;213:25-8
103. Nandagopal R, Moorthy SGK. Dramatic levodopa responsiveness of dystonia in a sporadic case of spinocerebellar ataxia type 3. Postgrad Med J 2004;80:363-5
104. Nunes M, Martinez A, Lopes-Cendes I, et al. Dystonia in Machado-Joseph disease: clinical features and levodopa response (P6.051). Neurology 2014;82(10 Suppl):P6.051-1
105. Buhmann C, Bussopulos A, Oechsner M. Dopaminergic response in Parkinsonian phenotype of Machado-Joseph disease. Mov Disord 2003;18:219-21
106. Lu C-S, Chang H-C, Kuo P-C, et al. The parkinsonian phenotype of spinocerebellar ataxia type 3 in a Taiwanese family. Parkinsonism Relat Disord 2004;10:369-73
107. Vogel AP, Folker J, Poole ML. Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes. Cochrane Database Syst Rev 2014;10:CD008953
108. Silva RC, Saute JA, Silva AC, et al. Occupational therapy in spinocerebellar ataxia type 3: an open-label trial. Braz J Med Biol Res 2010;43:537-42
109. França MC, D?Abreu A, Nucci A, Lopes-Cendes I. Muscle excitability abnormalities in Machado-Joseph disease. Arch Neurol 2008;65:525-9
110. Kanai K, Kuwabara S, Arai K, et al. Muscle cramp in Machado-Joseph disease: altered motor axonal excitability properties and mexiletine treatment. Brain 2003;126:965-73
111. França MC, D?Abreu A, Friedman JH, et al. Chronic pain in Machado-Joseph disease: a frequent and disabling symptom. Arch Neurol 2007;64:1767-70
112. Takei A, Okawa M, Sasaki H, et al. [Effective melatonin therapy in a case of Machado-Joseph disease with insomnia]. Rinsho Shinkeigaku 2000;40:736-40
113. López-Bastida J, Perestelo-Perez L, Montón-Alvarez F, Serrano-Aguilar P. Social economic costs and health-related quality of life in patients with degenerative cerebellar ataxia in Spain. Mov Disord 2008;23:212-17
114. Nguyen HP, Hübener J, Weber JJ, et al. Cerebellar soluble mutant ataxin-3 level decreases during disease progression in Spinocerebellar Ataxia Type 3 mice. PLoS One 2013;8:e62043
115. Alves S, Nascimento-Ferreira I, Auregan G, et al. Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado-Joseph disease. PLoS One 2008;3:e3341
116. Rodrguez-Lebrón E, Costa Mdo C, Luna-Cancalon K, et al. Silencing mutant ATXN3 expression resolves molecular phenotypes in SCA3 transgenic mice. Mol Ther 2013;21:1909-18
117. Evers MM, Tran H-D, Zalachoras I, et al. Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon. Neurobiol Dis 2013;58:49-56
118. Coelho T, Adams D, Silva A, et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med 2013;369:819-29
119. Miller TM, Pestronk A, David W, 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;12:435-42
120. Mendonça LS, Nóbrega C, Hirai H, et al. Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in Machado-Joseph disease mice. Brain 2015;138(Pt 2):320-35
121. Sakai T, Kawakami H. Machado-Joseph disease: a proposal of spastic paraplegic subtype. Neurology 1996;46:846-7
122. Tuite PJ, Rogaeva EA, St George-Hyslop PH, Lang AE. Dopa-responsive parkinsonism phenotype of Machado-Joseph disease: confirmation of 14q CAG expansion. Ann Neurol 1995;38:684-7
123. Van Schaik IN, Jöbsis GJ, Vermeulen M, et al. Machado-Joseph disease presenting as severe asymmetric proximal neuropathy. J Neurol Neurosurg Psychiatry 1997;63(4):534-6
124. Schöls L, Haan J, Riess O, et al. Sleep disturbance in spinocerebellar ataxias: is the SCA3 mutation a cause of restless legs syndrome? Neurology 1998;51:1603-7
125. D?Abreu A, França M, Conz L, et al. Sleep symptoms and their clinical correlates in Machado-Joseph disease. Acta Neurol Scand 2009;119:277-80
126. Pedroso JL, Braga-Neto P, Felício AC, et al. Sleep disorders in machado-joseph disease: frequency, discriminative thresholds, predictive values, and correlation with ataxia-related motor and non-motor features. Cerebellum 2011;10:291-5
127. Braga-Neto P, Felicio AC, Hoexter MQ, et al. Cognitive and olfactory deficits in Machado-Joseph disease: a dopamine transporter study. Parkinsonism Relat Disord 2012;18:854-8
128. Saute JA, da Silva AC, Donis KC, et al. Depressive mood is associated with ataxic and non-ataxic neurological dysfunction in SCA3 patients. Cerebellum 2010;9:603-5
129. Brusse E, Brusse-Keizer MG, Duivenvoorden HJ, van Swieten JC. Fatigue in spinocerebellar ataxia: patient self-assessment of an early and disabling symptom. Neurology 2011;76:953-9
130. Saute JA, Silva AC, Souza GN, et al. Body mass index is inversely correlated with the expanded CAG repeat length in SCA3/MJD patients. Cerebellum 2012;11:771-4; Erratum in: Cerebellum. 2012;11(3):775-6
131. De Rezende TJ, D?Abreu A, Guimara?es RP, et al. Cerebral cortex involvement in Machado-Joseph disease. Eur J Neurol 2015;22(2):277-83
132. Guimara?es RP, D?Abreu A, Yasuda CL, et al. A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3. Mov Disord 2013;28:1125-32
133. Fahl CN, Branco LM, Bergo FP, et al. Spinal cord damage in Machado-Joseph Disease. Cerebellum 2015;14(2):128-32
134. Lirng J-F, Wang P-S, Chen H-C, et al. Differences between spinocerebellar ataxias and multiple system atrophycerebellar type on proton magnetic resonance spectroscopy. PLoS One 2012;7:e47925
135. Lei L, Liao Y, Liao W, et al. Magnetic resonance spectroscopy of the cerebellum in patients with spinocerebellar ataxia type 3/Machado-Joseph disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2011;36:511-19
136. D?Abreu A, França MC, Yasuda CL, et al. Neocortical atrophy in Machado-Joseph disease: a longitudinal neuroimaging study. J Neuroimaging 2012;22:285-91
137. Öz G, Kittelson E, Demirgöz D, et al. Assessing recovery from neurodegeneration in spinocerebellar ataxia 1: comparison of in vivo magnetic resonance spectroscopy with motor testing, gene expression and histology. Neurobiol Dis 2014;74:158-66
138. Wüllner U, Reimold M, Abele M, et al. Dopamine transporter positron emission tomography in spinocerebellar ataxias type 1, 2, 3, and 6. Arch Neurol 2005;62(8):1280-5
139. C França M, D?abreu A, Nucci A, et al. Prospective study of peripheral neuropathy in Machado-Joseph disease. Muscle Nerve 2009;40:1012-18
140. La Spada AR, Wilson EM, Lubahn DB, et al. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991;352:77-9
141. Ikeda H, Yamaguchi M, Sugai S, et al. Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nat Genet 1996;13:196-202