Biomarkers for Huntington's disease: an update

Scahill, Rachael I.; Wild, Edward J.; Tabrizi, Sarah J.

doi:10.1517/17530059.2012.701205

Cited by 10 publications

(7 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the ubiquitous expression of mutant huntingtin, the development of biochemical biofluid biomarkers for HD has proved challenging. 112 Hypothesis-driven and 'omics' discovery approaches have yielded a multitude of candidate biomarkers, 113,114 but none can be said to have been 'validated'. 112 An example of the difficulties is 8-hydroxydeoxyguanosine (8OHdG), a product of oxidative DNA damage, which was reported to be elevated in plasma from patients with HD, and to be responsive to treatment with the antioxidant creatine.…”

Section: Other Biomarkersmentioning

confidence: 99%

Huntington disease: natural history, biomarkers and prospects for therapeutics

Aylward²,

et al. 2014

View full text Add to dashboard Cite

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials.

show abstract

Section: Other Biomarkersmentioning

confidence: 99%

Huntington disease: natural history, biomarkers and prospects for therapeutics

Aylward²,

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In the search for biomarkers, cerebrospinal fluid (CSF) has an advantage over blood because of its proximity to the neurodegenerative process. Biomarkers are needed in clinical trials due to the slow disease progression and the limitations of clinical assessment [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Tau or neurofilament light—Which is the more suitable biomarker for Huntington’s disease?

et al. 2017

View full text Add to dashboard Cite

IntroductionPrevious studies have suggested cerebrospinal fluid (CSF) levels of neurofilament light (NFL) and total tau are elevated in Huntington’s disease (HD) and may be used as markers of disease stage. Biomarkers are needed due to the slow disease progression and the limitations of clinical assessment. This study aims to validate the role of NFL and tau as biomarkers in HD.MethodsCSF was obtained from a cohort of HD patients and premanifest HD-mutation carriers. Unified Huntington’s Disease Rating Scale (UHDRS) testing was performed on all subjects at the time of sampling. NFL and tau concentrations were determined by ELISA. Spearman correlations were calculated with R version 3.2.3.Results11 premanifest HD and 12 manifest HD subjects were enrolled. NFL and tau levels were correlated. NFL showed strong correlations with all items included in the clinical assessment (for example the total functional capacity (TFC) (r = - 0.70 p < 0.01) and total motor score (TMS) (r = 0.83p < 0.01). Tau showed slightly weaker correlations (eg. TMS (r = 0.67 p < 0.01); TFC (r = - 0.59 p < 0.01)). NFL was significantly correlated with 5-year probability of disease onset, whereas tau was not.ConclusionThis study strengthens the case for NFL as a useful biomarker of disease stage. NFL was strongly correlated to all evaluated items in the UHDRS assessment. Tau also has a potential for use as a biomarker but correlations to clinical tests are weaker in this study. We suggest that NFL and possibly tau be used in clinical drug trials as biomarkers of disease progression that are potentially influenced by future disease-modifying therapies.

show abstract

“…Huntington’s disease (HD) is caused by an expansion repeat mutation in the Htt gene, which encodes a ubiquitously expressed 3144 amino acid protein of unknown function, leading to a toxic gain of function in the mutant protein [80], which promotes aberrant nuclear-cytoplasmic trafficking of the master neuronal regulator REST. The result is the deregulation of REST target gene expression in tissues from animal models of HD and human HD, which include both protein-coding genes as well as ncRNAs, such as lncRNAs.…”

Section: Role Of Lncrnas In the Central Nervous Systemmentioning

confidence: 99%

An Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders

Fenoglio

Ridolfi

Galimberti

et al. 2013

IJMS

View full text Add to dashboard Cite

A novel class of transcripts, long non coding RNAs (lncRNAs), has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, which still are to be elucidated. LncRNAs are pervasively transcribed in the genome and several lines of evidence correlate dysregulation of different lncRNAs to human diseases including neurological disorders. Although their mechanisms of action are yet to be fully elucidated, evidence suggests lncRNA contributions to the pathogenesis of a number of diseases. In this review, the current state of knowledge linking lncRNAs to different neurological disorders is discussed and potential future directions are considered.

show abstract

Biomarkers for Huntington's disease: an update

Cited by 10 publications

References 22 publications

Huntington disease: natural history, biomarkers and prospects for therapeutics

Huntington disease: natural history, biomarkers and prospects for therapeutics

Tau or neurofilament light—Which is the more suitable biomarker for Huntington’s disease?

An Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders

Contact Info

Product

Resources

About