George Huntington: a legacy of inquiry, empathy and hope

Wexler, Alice; Wild, Edward J.; Tabrizi, Sarah J.

doi:10.1093/brain/aww165

Cited by 37 publications

(35 citation statements)

References 12 publications

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“…He described its hereditary nature, associated psychiatric and cognitive symptoms and the manifestation of the disease in adult life between 30 and 40 years of age. He outlined the progressive nature of the disease stating, ‘Once it begins it clings to the bitter end’ . However, the monogenic nature and full penetrance of HD makes it perhaps one of the most treatable neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Huntington's disease: a clinical review

McColgan

Tabrizi

2017

Euro J of Neurology

777

645

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Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6–13.7 individuals per 100 000. It is characterized by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein. Early macroscopic changes are seen in the striatum with involvement of the cortex as the disease progresses. There are currently no disease modifying treatments; therefore supportive and symptomatic management is the mainstay of treatment. In recent years there have been significant advances in understanding both the cellular pathology and the macroscopic structural brain changes that occur as the disease progresses. In the last decade there has been a large growth in potential therapeutic targets and clinical trials. Perhaps the most promising of these are the emerging therapies aimed at lowering levels of mutant huntingtin. Antisense oligonucleotide therapy is one such approach with clinical trials currently under way. This may bring us one step closer to treating and potentially preventing this devastating condition.

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Section: Introductionmentioning

confidence: 99%

Huntington's disease: a clinical review

McColgan

Tabrizi

2017

Euro J of Neurology

777

645

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“…HD has a relatively low occurrence: around 10.6-13.7 individuals per 100,000 in western populations, and 1-7 individuals per million in Asian populations [ 7 ]. Even so, George Huntington, the person who first defined the disease in 1872, described it as follows: “Once it begins, it clings to the bitter end” [ 8 ]. There is currently no cure for HD [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Rhythmic Haptic Cueing Using Wearable Devices as Physiotherapy for Huntington Disease: Case Study

Georgiou¹,

Islam²,

Holland³

et al. 2020

JMIR Rehabil Assist Technol

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Background Huntington disease (HD) is an inherited genetic disorder that results in the death of brain cells. HD symptoms generally start with subtle changes in mood and mental abilities; they then degenerate progressively, ensuing a general lack of coordination and an unsteady gait, ultimately resulting in death. There is currently no cure for HD. Walking cued by an external, usually auditory, rhythm has been shown to steady gait and help with movement coordination in other neurological conditions. More recently, work with other neurological conditions has demonstrated that haptic (ie, tactile) rhythmic cues, as opposed to audio cues, offer similar improvements when walking. An added benefit is that less intrusive, more private cues are delivered by a wearable device that leaves the ears free for conversation, situation awareness, and safety. This paper presents a case study where rhythmic haptic cueing (RHC) was applied to one person with HD. The case study has two elements: the gait data we collected from our wearable devices and the comments we received from a group of highly trained expert physiotherapists and specialists in HD. Objective The objective of this case study was to investigate whether RHC can be applied to improve gait coordination and limb control in people living with HD. While not offering a cure, therapeutic outcomes may delay the onset or severity of symptoms, with the potential to improve and prolong quality of life. Methods The approach adopted for this study includes two elements, one quantitative and one qualitative. The first is a repeated-measures design with three conditions: before haptic rhythm (ie, baseline), with haptic rhythm, and after exposure to haptic rhythm. The second element is an in-depth interview with physiotherapists observing the session. Results In comparison to the baseline, the physiotherapists noted a number of improvements to the participant’s kinematics during her walk with the haptic cues. These improvements continued in the after-cue condition, indicating some lasting effects. The quantitative data obtained support the physiotherapists’ observations. Conclusions The findings from this small case study, with a single participant, suggest that a haptic metronomic rhythm may have immediate, potentially therapeutic benefits for the walking kinematics of people living with HD and warrants further investigation.

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“…With the antisense oligonucleotide (ASO) huntingtin lowering trial (7) currently underway, there is an urgent need to understand the time course of white matter changes and the mechanisms that drive them so that brain areas can be identified that may benefit from the highest concentrations of ASO.…”

Section: Introductionmentioning

confidence: 99%

Topological length of white matter connections predicts their rate of atrophy in premanifest Huntington’s disease

McColgan

Seunarine²,

Gregory

et al. 2017

JCI Insight

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We lack a mechanistic explanation for the stereotyped pattern of white matter loss seen in Huntington’s disease (HD). While the earliest white matter changes are seen around the striatum, within the corpus callosum, and in the posterior white matter tracts, the order in which these changes occur and why these white matter connections are specifically vulnerable is unclear. Here, we use diffusion tractography in a longitudinal cohort of individuals yet to develop clinical symptoms of HD to identify a hierarchy of vulnerability, where the topological length of white matter connections between a brain area and its neighbors predicts the rate of atrophy over 24 months. This demonstrates a new principle underlying neurodegeneration in HD, whereby brain connections with the greatest topological length are the first to suffer damage that can account for the stereotyped pattern of white matter loss observed in premanifest HD.

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George Huntington: a legacy of inquiry, empathy and hope

Cited by 37 publications

References 12 publications

Huntington's disease: a clinical review

Huntington's disease: a clinical review

Rhythmic Haptic Cueing Using Wearable Devices as Physiotherapy for Huntington Disease: Case Study

Topological length of white matter connections predicts their rate of atrophy in premanifest Huntington’s disease

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