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Instituto Nacional de Neurología y Neurocirugía

2022, Number 4

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Arch Neurocien 2022; 27 (4)

Current knowledge and future directions in Huntington’s disease

Morales E, Herrera C, Montaño L, Martínez K, Meza M, Del Villar N, Mendoza X, Rodríguez A

Language: English
References: 89
Page: 31-43
PDF size: 597.70 Kb.


ABSTRACT

Huntington’s disease (HD) is an inherited neurodegenerative disorder due to abnormal CAG triplet repeats in the IT-15 gene. It is characterized by a triad of progressive motor, psychiatric and cognitive symptoms resulting from striatal neuronal loss. HD is most prevalent in Western countries, and a particularly high prevalence in Latin America has been reported. In this article, we present a state-ofthe- art review of HD, including the identification of different polymorphic markers in the genes coding for UCHL1, HIP1, PGC1α, GRIK2, TBP, BDNF, and ZDHHC17, which could be associated with the age at onset of motor signs in the presence of abnormal CAG repeats.
Despite significant advances in our understanding of the disease, there are still gaps in the comprehension of its pathophysiology, and there is no effective therapeutic target to prevent the clinical onset of the disease or delay its progression. Current pharmacological management is palliative, and the evidence to generalize surgical approaches such as pallidotomy is insufficient. Recently, different therapies that target neurodegeneration and the synthesis of mutant Huntingtin (mHtt) have shown promise, as well as fetal neural cell transplantation into the striatum, which is offered as a surgical option providing hope for the development of a true disease-modifying treatment that allows the recovery of motor and cognitive functions through anatomical and functional integration of grafted neurons.
This narrative review aims to provide an approach to HD’s most relevant aspects, from its pathogenesis and associated genetic polymorphisms to current treatment options.


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