What is the impact of education on Huntington's disease?

Background: The relative contribution of grey matter (GM) and white matter (WM) degeneration to the progressive brain atrophy in Huntington’s disease (HD) has been well studied. The pathology of the spinal cord in HD is comparatively less well documented. Objective: We aim to characterize spinal cord WM abnormalities in a mouse model of HD and evaluate whether selective removal of mutant huntingtin (mHTT) from oligodendroglia rescues these deficits. Methods: Histological assessments were used to determine the area of GM and WM in the spinal cord of 12-month-old BACHD mice, while electron microscopy was used to analyze myelin fibers in the cervical area of the spinal cord. To investigate the impact of inactivation of mHTT in oligodendroglia on these measures, we used the previously described BACHDxNG2Cre mouse line where mHTT is specifically reduced in oligodendrocyte progenitor cells. Results: We show that spinal GM and WM areas are significantly atrophied in HD mice compared to wild-type controls. We further demonstrate that specific reduction of mHTT in oligodendroglial cells rescues the atrophy of spinal cord WM, but not GM, observed in HD mice. Inactivation of mHTT in oligodendroglia had no effect on the density of oligodendroglial cells but enhanced the expression of myelin-related proteins in the spinal cord. Conclusion: Our findings demonstrate that the myelination abnormalities observed in brain WM structures in HD extend to the spinal cord and suggest that specific expression of mHTT in oligodendrocytes contributes to such abnormalities.

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Characterising Upper Limb Movements in Huntington's Disease and the Impact of Restricted Visual Cues

PLoS ONE ◽

10.1371/journal.pone.0133709 ◽

2015 ◽

Vol 10 (8) ◽

pp. e0133709 ◽

Cited By ~ 2

Author(s):

Jessica Despard ◽

Anne-Marie Ternes ◽

Bleydy Dimech-Betancourt ◽

Govinda Poudel ◽

Andrew Churchyard ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Upper Limb ◽

Visual Cues ◽

Limb Movements ◽

Upper Limb Movements ◽

The Impact

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The impact of the gut microbiota on Huntington's disease mice

IBRO Reports ◽

10.1016/j.ibror.2019.07.1177 ◽

2019 ◽

Vol 6 ◽

pp. S370-S371

Author(s):

Carolina De Moura Gubert ◽

Geraldine Kong ◽

Jamie Liew ◽

Chloe Love ◽

Thibault Renoir ◽

...

Keyword(s):

Gut Microbiota ◽

Huntington's Disease ◽

Huntington’S Disease ◽

The Impact

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IKKβ slows Huntington’s disease progression in R6/1 mice

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1814246116 ◽

2019 ◽

Vol 116 (22) ◽

pp. 10952-10961 ◽

Cited By ~ 4

Author(s):

Joseph Ochaba ◽

Gianna Fote ◽

Marketta Kachemov ◽

Soe Thein ◽

Sylvia Y. Yeung ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Neuronal Degeneration ◽

Neuronal Injury ◽

Therapeutic Interventions ◽

Striatal Neurons ◽

Microglial Response ◽

Relationship Of ◽

The Impact

Neuroinflammation is an important contributor to neuronal pathology and death in neurodegenerative diseases and neuronal injury. Therapeutic interventions blocking the activity of the inflammatory kinase IKKβ, a key regulator of neuroinflammatory pathways, is protective in several animal models of neurodegenerative disease and neuronal injury. In Huntington’s disease (HD), however, significant questions exist as to the impact of blocking or diminishing the activity of IKKβ on HD pathology given its potential role in Huntingtin (HTT) degradation. In cell culture, IKKβ phosphorylates HTT serine (S) 13 and activates HTT degradation, a process that becomes impaired with polyQ expansion. To investigate the in vivo relationship of IKKβ to HTT S13 phosphorylation and HD progression, we crossed conditional tamoxifen-inducible IKKβ knockout mice with R6/1 HD mice. Behavioral assays in these mice showed a significant worsening of HD pathological phenotypes. The increased behavioral pathology correlated with reduced levels of endogenous mouse full-length phospho-S13 HTT, supporting the importance of IKKβ in the phosphorylation of HTT S13 in vivo. Notably, many striatal autophagy genes were up-regulated in HD vs. control mice; however, IKKβ knockout partially reduced this up-regulation in HD, increased striatal neurodegeneration, and enhanced an activated microglial response. We propose that IKKβ is protective in striatal neurons early in HD progression via phosphorylation of HTT S13. As IKKβ is also required for up-regulation of some autophagy genes and HTT is a scaffold for selective autophagy, IKKβ may influence autophagy through multiple mechanisms to maintain healthy striatal function, thereby reducing neuronal degeneration to slow HD onset.

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The impact of an intense religious experience on motor symptoms in Huntington's disease

Movement Disorders ◽

10.1002/mds.22405 ◽

2008 ◽

Vol 24 (3) ◽

pp. 473-474 ◽

Cited By ~ 1

Author(s):

Jose Luis López-Sendón Moreno ◽

Justo Garcia de Yebenes

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Religious Experience ◽

Motor Symptoms ◽

The Impact

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The Impact of Juvenile Huntington's Disease on the Family

Journal of Health Psychology ◽

10.1177/1359105307084307 ◽

2008 ◽

Vol 13 (1) ◽

pp. 5-16 ◽

Cited By ~ 18

Author(s):

Helen M. Brewer ◽

Virginia Eatough ◽

Jonathan A. Smith ◽

Cath A. Stanley ◽

Neil W. Glendinning ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

The Family ◽

Juvenile Huntington’S Disease ◽

The Impact

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The impact of occipital lobe cortical thickness on cognitive task performance: An investigation in Huntington's Disease

Neuropsychologia ◽

10.1016/j.neuropsychologia.2015.10.033 ◽

2015 ◽

Vol 79 ◽

pp. 138-146 ◽

Cited By ~ 30

Author(s):

Eileanoir B. Johnson ◽

Elin M. Rees ◽

Izelle Labuschagne ◽

Alexandra Durr ◽

Blair R. Leavitt ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Task Performance ◽

Cortical Thickness ◽

Cognitive Task ◽

Occipital Lobe ◽

Cognitive Task Performance ◽

The Impact

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Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease

Psychological Medicine ◽

10.1017/s0033291714000579 ◽

2014 ◽

Vol 44 (15) ◽

pp. 3341-3356 ◽

Cited By ~ 30

Author(s):

R. C. Wolf ◽

F. Sambataro ◽

N. Vasic ◽

M. S. Depping ◽

P. A. Thomann ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Motor Function ◽

Neural Activity ◽

Resting State ◽

Brain Atrophy ◽

Clinical Symptoms ◽

Resting State Fmri ◽

Cognitive Networks ◽

The Impact

Background.Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's ‘resting state’ could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients.Method.Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and ‘biological parametric mapping’ analyses to investigate the impact of atrophy on neural activity.Results.Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition.Conclusions.This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

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Analysis of the impact of Tominersen (IONIS-HTTRX/RG6042) in the treatment of Huntington’s disease: A systematic review

10.5327/1516-3180.046 ◽

2021 ◽

Author(s):

Gustavo Soares Gomes Barros Fonseca ◽

Maria Luiza Mendes Machado ◽

Paulo Victor Protásio Bezerra

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Messenger Rna ◽

Randomized Clinical Trials ◽

Therapeutic Response ◽

Gene Encoding ◽

Double Blind ◽

Electronic Search ◽

The Impact ◽

To Receive

Introduction: Huntington’s disease (HD) is a congenital pathology of a hereditary, neurodegenerative and progressive character, with a high mortality rate. This pathology is caused by repeated expansions of a single CAG codon in the gene encoding huntingtin. To date, several attempts to prevent and delay such a mutation have been carried out in patients. However, a promising drug, Tominersen, formerly called IONIS HTTRx/ RG6042, is in the testing phase and has shown a favorable therapeutic response, which acts directly on the messenger RNA of the gene encoding huntingtin (HTT). The drug, whose route of administration is intrathecal in bolus, intercepts and destroys the messenger before the corrupted protein can work. The present study aims to analyze the impact of Tominersen in the treatment of patients with HD and to evaluate its prognosis. Methods: The present study is a systematic literature review, in which an electronic search was performed in the PubMed, SciELO, Web of Science and Google Scholar databases. Results: In one of the double-blind randomized clinical trials (n = 46), 34 were assigned to receive the drug. The group that received Tominersen showed a decrease in the concentration of mutant HTT in cerebrospinal fluid after 28 days. In another study (n = 791), the GENERATION HD1 clinical trial is currently taking place and will last for 25 months. Conclusion: Tominersen decreases the concentration of HTT, that is, it suppressed the protein responsible for HD. Studies related to the drug are still very recent and require extra attention.

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