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Biomarkers in Huntington’s Disease

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Neurodegenerative Diseases Biomarkers

Part of the book series: Neuromethods ((NM,volume 173))

Abstract

Huntington’s disease (HD) is a neurodegenerative disorder caused by a trinucleotide repeat expansion mutation. The expansion length is the diagnostic biomarker for the disease. It can result in four different scenarios depending on its number of repeats: the intermediate allele, adult onset disease with either reduced or full penetrance, and juvenile HD. Along with various genetic modifiers, the mutation predicts the age of clinical onset. By convention, the clinical diagnosis of HD is reached when there is sufficient motor dysfunction, as judged by the Unified HD Rating Scale. This scale is widely used in clinical trials, but is limited by its subjectivity, categorical ratings, and insensitivity to subtle features in early disease. The need for sensitive, objective, continuous biomarkers has heralded a wave of digital biomarkers, which range from devices embedded with force transducers to smartphone applications. These have become a standard component of clinical trial assessments. However, they provide no insight into the pathological status of the disease. Certain wet biomarkers can identify the earliest indication of pathological change, when disease-modifying therapy would ideally be initiated to prevent or delay the clinical manifestations of the disease. Such treatments are being developed, but their evaluation in subjects with minimal clinical findings will depend on sensitive pathological biomarkers of progression. The most promising protein biomarkers are neurofilament light chain and mutant huntingtin, the latter having shown utility as a pharmacodynamic biomarker for a novel huntingtin-lowering treatment. Of the genetic biomarkers, certain microRNAs and telomere length have proven to be early indicators of pathological change. These are discussed, along with other biomarker candidates.

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Authors and Affiliations

  1. Department of Neurology, University of Iowa Hospital and Clinics, Iowa City, IA, USA

    Annie Killoran

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  1. Annie Killoran
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Correspondence to Annie Killoran .

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  1. Department of Anatomy, University of Otago, Dunedin, New Zealand

    Philip V. Peplow

  2. Department of Pharmacology, Department of Medicine, Reno School of Medicine, University of Nevada, Reno, NV, USA

    Bridget Martinez

  3. Department of Neurosurgery, George Washington University, West Chester, PA, USA

    Thomas A. Gennarelli

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Killoran, A. (2022). Biomarkers in Huntington’s Disease . In: Peplow, P.V., Martinez, B., Gennarelli, T.A. (eds) Neurodegenerative Diseases Biomarkers. Neuromethods, vol 173. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1712-0_10

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