Huntington’s Disease Community Perspectives on Desired Characteristics of Disease Modifying Therapies

Background: Huntington’s disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. A toxic accumulation of misfolded mutant huntingtin protein (Htt) induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. Improving mitochondrial function has been proposed as an opportunity to treat HD, but it is not known how mitochondrial function in different tissues relates. Objective: We explored associations between central and peripheral mitochondrial function in a group of mild to moderate staged HD patients. Methods: We used phosphorous magnetic resonance spectroscopy (31P-MRS) to measure mitochondrial function in vivo in the calf muscle (peripheral) and the bio-energetic state in the visual cortex (central). Mitochondrial function was also assessed ex vivo in circulating peripheral blood mononuclear cells (PBMCs). Clinical function was determined by the Unified Huntington’s Disease Rating Scale (UHDRS) total motor score. Pearson correlation coefficients were computed to assess the correlation between the different variables. Results: We included 23 manifest HD patients for analysis. There was no significant correlation between central bio-energetics and peripheral mitochondrial function. Central mitochondrial function at rest correlated significantly to the UHDRS total motor score (R = –0.45 and –0.48), which increased in a subgroup with the largest number of CAG repeats. Discussion: We did not observe a correlation between peripheral and central mitochondrial function. Central, but not peripheral, mitochondrial function correlated to clinical function. Muscle mitochondrial function is a promising biomarker to evaluate disease-modifying compounds that improve mitochondrial function, but Huntington researchers should use central mitochondrial function to demonstrate proof-of-pharmacology of disease-modifying compounds.

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Huntington's Disease—community care? A carer's tale

Journal of Public Health ◽

10.1093/oxfordjournals.pubmed.a042777 ◽

1992 ◽

Vol 14 (4) ◽

pp. 385-388 ◽

Cited By ~ 2

Author(s):

Joyce Gilbert

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Community Care ◽

Disease Community

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Positive Attitudes and Therapeutic Misconception Around Hypothetical Clinical Trial Participation in the Huntington’s Disease Community

Journal of Huntington s Disease ◽

10.3233/jhd-190382 ◽

2019 ◽

Vol 8 (4) ◽

pp. 421-430 ◽

Cited By ~ 2

Author(s):

Kristina Cotter ◽

Carly E. Siskind ◽

Sharon J. Sha ◽

Andrea K. Hanson-Kahn

Keyword(s):

Clinical Trial ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Trial Participation ◽

Therapeutic Misconception ◽

Clinical Trial Participation ◽

Positive Attitudes ◽

Disease Community

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Huntington’s disease

Oxford Textbook of Neurologic and Neuropsychiatric Epidemiology ◽

10.1093/med/9780198749493.003.0010 ◽

2020 ◽

pp. 83-92

Author(s):

Juliana R Dutra ◽

Tanya P Garcia ◽

Karen Marder

Keyword(s):

Clinical Trials ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Trinucleotide Repeat ◽

Neurodegenerative Disorder ◽

Genetic Mutation ◽

Current Standard ◽

Disease Modifying ◽

Disease Modifying Agents ◽

A Current

Huntington’s disease (HD) is an autosomal dominant, neurodegenerative disorder caused by an unstable expansion in the cytosine adenine guanine (CAG) trinucleotide repeat in the huntingtin gene. The disease onsets gradually over many years and its symptoms include extrapyramidal movement disorder, cognitive impairment, and behavioural changes. Understanding the overall progression of HD is critical to designing clinical trials with possible disease modifying agents. Research in this area has exploded in the past two decades, as different multicentre studies have evaluated both clinical and biological measures in individuals at different stages of the disease (i.e. at-risk for the genetic mutation, pre-manifest, and manifest HD). In this chapter, we provide readers with a current understanding of HD progression. This includes an overview of the current standard for how HD is clinically evaluated, descriptive epidemiology of the disease, genetics of HD, and a review of potential disease modifiers.

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