Current Knowledge and Future Directions in Huntington’s Disease
DOI:
https://doi.org/10.31157/an.v27i4.346Keywords:
Age at onset, Huntington disease, Htt protein, PolymorphismAbstract
Introduction: Huntington's Disease (HD) is a hereditary, neurodegenerative disorder due to abnormal repeats of the CAG triplet in the IT-15 gene. It is characterized by a triad of progressive motor, psychiatric and cognitive symptoms, resulting from striatal neuronal loss. The impact of HD in Latin America is evidenced by the prevalence rates in Maracaibo (Venezuela) and Juan de Acosta (Colombia), which are the highest recorded in the world. This contrasts with the social abandonment and the scarce intervention of local governments.
Aim: Provide an approach to the most relevant aspects of HD from its pathogenesis and associated genetic polymorphisms, to the current treatment options.
Methodology: A literature review was performed of the state of the art of prognosis and treatment strategies in HD, including the identification of different polymorphic markers in the genes coding for UCHL1, HIP1, PGC1α, GRIK2, TBP, BDNF, among others, and its associations in the evolution of the disease in the presence of abnormal CAG repeats.
Conclusion: Even though in the last decades many researchers have focused on the development of curative treatment, there is no effective therapeutic target to prevent the clinical onset of the disease or to delay its progression. Instead, current pharmacological management is palliative, the evidence to generalize the surgical approaches is insufficient. Newly, the fetal neural cell transplantation into the striatum is offered as the surgical option that provides hope for the development of a true disease-modifying treatment.
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4. Migliore S, Jankovic J, Squitieri F. Genetic counseling in Huntington’s disease: Potential new challenges on horizon? Front Neurol. 2019;10(APR):1–6. DOI: 10.3389/fneur.2019.00453
5. Massey TH, Jones L. The central role of DNA damage and repair in CAG repeat diseases. DMM Dis Model Mech. 2018;11(1). DOI: 10.1242/dmm.031930
6. Chao T-K, Hu J, Pringsheim T. Risk factors for the onset and progression of Huntington disease. Neurotoxicology [Internet]. 2017;61:79–99. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0161813X17300165 DOI: 10.1016/j.neuro.2017.01.005
7. Castilhos R, Augustin M, Santos J, Perandones C, Saraiva-Pereira M, Jardim L. Genetic aspects of Huntington’s disease in Latin America. A systematic review on Behalf of Rede Neurogenética. Clin Genet. 2016;89(89):295–303. DOI: 10.1111/cge.12641
8. Cascante L. Análisis de un caso y revisión bibliográfica sobre síntomas psiquiátricos prodrómicos en la Enfermedad de Huntington. Universidad de Costa Rica; 2018.
9. Walker RH, Gatto EM, Bustamante ML, Bernal-Pacheco O, Cardoso F, Castilhos RM, et al. Huntington’s disease-like disorders in Latin America and the Caribbean. Park Relat Disord. 2018;53:10–20. DOI: 10.1016/j.parkreldis.2018.05.021
10. Silva-Paredes G, Urbanos-Garrido RM, Inca-Martinez M, Rabinowitz D, Cornejo-Olivas MR. Economic burden of Huntington’s disease in Peru. BMC Health Serv Res. 2019;19(1):1–10. DOI: 10.1186/s12913-019-4806-6
11. Daniel C, Sepúlveda R, Sierra García N. Enfermedad De Huntington: Estado Del Arte. 2014;
12. Campo M del C, Bute LE. Vulnerable Groups, The Responsibility Of The State To Guarantee The Right To Health: Huntington In Communities Of The Caribbean Region Of Colombia. Perfiles las Ciencias Soc. 2016;3(6):54–99.
13. Raymond LA, André VM, Cepeda C, Gladding CM, Milnerwood AJ, Levine AMS. REVIEW PATHOPHYSIOLOGY OF HUNTINGTON’S DISEASE: TIME-DEPENDENT ALTERATIONS IN SYNAPTIC AND RECEPTOR FUNCTION. NSC. 2011;198:252–73. DOI: 10.1016/j.neuroscience.2011.08.052
14. Blumenstock S, Dudanova I. Cortical and Striatal Circuits in Huntington’s Disease. Front Neurosci. 2020;14(February). DOI: 10.3389/fnins.2020.00082
15. Tasset I, Sánchez F, Túnez I. Bases moleculares de la enfermedad de Huntington: Papel del estrés oxidativo. Rev Neurol. 2009;49(8):424–9. DOI: https://doi.org/10.33588/rn.4908.2009192
16. Plotkin JL, Goldberg JA. Thinking Outside the Box (and Arrow): Current Themes in Striatal Dysfunction in Movement Disorders. Neuroscientist. 2019;25(4):359–79. DOI: 10.1177/1073858418807887
17. De Paepe AE, Sierpowska J, Garcia-Gorro C, Martinez-Horta S, Perez-Perez J, Kulisevsky J, et al. White matter cortico-striatal tracts predict apathy subtypes in Huntington’s disease. NeuroImage Clin [Internet]. 2019;24(March):101965. Available from: https://doi.org/10.1016/j.nicl.2019.101965
18. Langbehn DR, Hayden MR, Paulsen JS, Johnson H, Aylward E, Biglan K, et al. CAG-repeat length and the age of onset in Huntington Disease (HD): A review and validation study of statistical approaches. Am J Med Genet Part B Neuropsychiatr Genet. 2010;153(2):397–408. DOI: 10.1002/ajmg.b.30992
19. Gusella JF, MacDonald ME, Lee J-M. Genetic modifiers of Huntington’s disease. Mov Disord [Internet]. 2014;29(11):1359–65. Available from: http://doi.wiley.com/10.1002/mds.26001 DOI: 10.1002/mds.26001
20. Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med. 2004. DOI: 10.1038/nm985
21. Metzger S, Bauer P, Tomiuk J, Laccone F, DiDonato S, Gellera C, et al. Genetic analysis of candidate genes modifying the age-at-onset in Huntington’s disease. Hum Genet. 2006;120(2):285–92. DOI:10.1007/s00439-006-0221-2
22. Metzger S, Bauer P, Tomiuk J, Laccone F, Didonato S, Gellera C, et al. The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington’s disease. Neurogenetics. 2006;7(1):27–30. DOI: 10.1007/s10048-005-0023-z
23. Xu E he, Tang Y, Li D, Jia J ping. Polymorphism of HD and UCHL-1 genes in Huntington’s disease. J Clin Neurosci [Internet]. 2009;16(11):1473–7. Available from: http://dx.doi.org/10.1016/j.jocn.2009.03.027 DOI: 10.1016/j.jocn.2009.03.027
24. Taherzadeh-Fard E, Saft C, Andrich J, Wieczorek S, Arning L. PGC-1alpha as modifier of onset age in Huntington disease. Mol Neurodegener. 2009;4(1):4–7. DOI: 10.1186/1750-1326-4-10
25. Moss DJH, Pardiñas AF, Langbehn D, Lo K, Leavitt BR, Roos R, et al. Identification of genetic variants associated with Huntington’s disease progression: a genome-wide association study. Lancet Neurol. 2017. DOI: 10.1016/S1474-4422(17)30161-8
26. Lee JH, Lee JM, Ramos EM, Gillis T, Mysore JS, Kishikawa S, et al. TAA repeat variation in the GRIK2 gene does not influence age at onset in Huntington’s disease. Biochem Biophys Res Commun [Internet]. 2012;424(3):404–8. Available from: http://dx.doi.org/10.1016/j.bbrc.2012.06.120. DOI: 10.1016/j.bbrc.2012.06.120
27. Alberch J, López M, Badenas C, Carrasco J, Milà M, Muñoz E, et al. Association between BDNF Val66Met polymorphism and age at onset in Huntington disease. Neurology. 2005. DOI: 10.1212/01.wnl.0000175977.57661.b1
28. Daza J, Coronell C, Brokate A, Caiaffa H, Alfonso H. Characterization of polymorphic sequences of CAG and CCG triplets of Huntington’s disease in Colombian families. 2006;
29. Ncheux C, Mouret J-F, Diirr A, Agid Y, Feingold J, Brice A, et al. Sequence analysis of the CCG polymorphic region adjacent to the CAG triplet repeat of the HD gene in normal and HD chromosomes. JMed Genet Genet. 1995;3232. DOI: 10.1136/jmg.32.5.399
30. Ghosh R, Tabrizi SJ. Clinical features of huntington’s disease. Adv Exp Med Biol. 2018;1049:1–28. DOI: 10.1007/978-3-319-71779-1_1
31. Cano M, Talavera V. Enfermedad de Huntington variedad Westphal: reporte de caso. 2015;16(163):52–7.
32. Dayalu P, Albin RL. Huntington Disease: Pathogenesis and Treatment. Neurol Clin. 2015;33(1):101–14. DOI: 10.1016/j.ncl.2014.09.003
33. Rodríguez J, Díaz V, Rojas Y, Rodríguez Y, Núñez E. Actualización en enfermedad de Huntington. Gen Univ Vladimir Ilich Lenin [Internet]. 2013;17(1):546–57. Available from: http://scielo.sld.cu/pdf/ccm/v17s1/ccm03513.pdf
34. Molano J, Iragorri A, Ucrós G, Bonilla C, Tovar S, Herin D, et al. Obsessive-Compulsive Disorder Symptoms in Huntington’s Disease: A Case Report. Rev Colomb Psiquiatr. 2008;37(4):644–54. DOI: 10.1901/jaba.2008.37-644
35. Shannon K, Hersch S. La enfermedad de Huntington: Serie de Guías Familiares. 1. Tarapata K, editor. New York.; 2010. 24 p.
36. Camargo-Mendoza M, Castillo-Triana N, Fandiño Cardona JM, Mateus-Moreno A, Moreno-Martínez M. Características del habla, el lenguaje y la deglución en la enfermedad de Huntington. Rev la Fac Med. 2017;65(2):343–8. DOI: http://dx.doi.org/10.15446/revfacmed.v65n2.57449
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2022-05-31
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Morales, E., Herrera , C., Montaño , L., Martínez, K., Meza, M., Del Villar, N., Mendoza, X., & Rodríguez, A. (2022). Current Knowledge and Future Directions in Huntington’s Disease. Archivos De Neurociencias, 27(4). https://doi.org/10.31157/an.v27i4.346
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Copyright (c) 2022 Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez
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January 2014-December 2021 © Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez. Open access articles under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
