scholarly journals Quantitative Electroencephalographic Analysis Provides an Early-Stage Indicator of Disease Onset and Progression in the zQ175 Knock-In Mouse Model of Huntington's Disease

SLEEP ◽  
2016 ◽  
Vol 39 (2) ◽  
pp. 379-391 ◽  
Author(s):  
Simon P. Fisher ◽  
Michael D. Schwartz ◽  
Sarah Wurts-Black ◽  
Alexia M. Thomas ◽  
Tsui-Ming Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Early Stage ◽  
Disease Onset

scholarly journals Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington’s Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

2021 ◽  
Author(s):  
Danielle A. Simmons ◽  
Brian D. Mills ◽  
Robert R. Butler III ◽  
Jason Kuan ◽  
Tyne L. M. McHugh ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Treatment Response ◽  
Diffusion Tensor ◽  
Disease Onset ◽  
Therapeutic Effects ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Pharmacodynamic Biomarkers

AbstractHuntington’s disease (HD) is caused by an expansion of the CAG repeat in the huntingtin gene leading to preferential neurodegeneration of the striatum. Disease-modifying treatments are not yet available to HD patients and their development would be facilitated by translatable pharmacodynamic biomarkers. Multi-modal magnetic resonance imaging (MRI) and plasma cytokines have been suggested as disease onset/progression biomarkers, but their ability to detect treatment efficacy is understudied. This study used the R6/2 mouse model of HD to assess if structural neuroimaging and biofluid assays can detect treatment response using as a prototype the small molecule p75NTR ligand LM11A-31, shown previously to reduce HD phenotypes in these mice. LM11A-31 alleviated volume reductions in multiple brain regions, including striatum, of vehicle-treated R6/2 mice relative to wild-types (WTs), as assessed with in vivo MRI. LM11A-31 also normalized changes in diffusion tensor imaging (DTI) metrics and diminished increases in certain plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6, in R6/2 mice. Finally, R6/2-vehicle mice had increased urinary levels of the p75NTR extracellular domain (ecd), a cleavage product released with pro-apoptotic ligand binding that detects the progression of other neurodegenerative diseases; LM11A-31 reduced this increase. These results are the first to show that urinary p75NTR-ecd levels are elevated in an HD mouse model and can be used to detect therapeutic effects. These data also indicate that multi-modal MRI and plasma cytokine levels may be effective pharmacodynamic biomarkers and that using combinations of these markers would be a viable and powerful option for clinical trials.

Neuropsychological manifestations of the genetic mutation for Huntington's disease in presymptomatic individuals

2002 ◽  
Vol 8 (7) ◽  
pp. 918-924 ◽  
Author(s):  
JASON BRANDT ◽  
BARNETT SHPRITZ ◽  
ANN MARIE CODORI ◽  
RUSSELL MARGOLIS ◽  
ADAM ROSENBLATT
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Early Stage ◽  
Age At Onset ◽  
Disease Onset ◽  
Signs And Symptoms ◽  
Genetic Mutation ◽  
Clinically Normal ◽  
Dementing Illness ◽  
Brain And Behavior

A triplet repeat (CAG) expansion mutation in the huntingtin gene on chromosome 4 is responsible for Huntington's disease (HD). Presymptomatic genetic testing for this mutation has identified clinically normal persons who are virtually certain to develop this dementing illness if they live a normal lifespan. The present study sought to determine whether these “mutation-positive” persons have impairments in cognitive functioning. Seventy-five mutation-positive persons did not differ from 128 mutation-negative persons on tests selected for their sensitivity to early-stage HD. Interestingly, however, those with the mutation viewed themselves as more likely to develop HD than did those without the mutation. Among mutation-positive subjects, having a longer CAG repeat mutation was likewise not associated with cognitive impairment. However, being closer to estimated disease onset (a product of repeat length and parent's age at onset) was associated with selected cognitive impairments. When viewed in light of previous studies showing atrophy of the caudate nucleus and putamen in mutation-carriers who are close to onset but not those far from onset, these results suggest that subtle changes in brain and behavior may be detected shortly before subjects with the HD mutation develop sufficient signs and symptoms for diagnosis. Conceptual and methodological problems associated with the search for presymptomatic cognitive and behavioral indicators of dementing illness are discussed. (JINS, 2002, 8, 918–924.)

Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data

2013 ◽  
Vol 12 (7) ◽  
pp. 637-649 ◽  
Author(s):  
Sarah J Tabrizi ◽  
Rachael I Scahill ◽  
Gail Owen ◽  
Alexandra Durr ◽  
Blair R Leavitt ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Observational Data ◽  
Early Stage ◽  
Disease Onset ◽  
Study Analysis

Speech acoustic markers of early stage and prodromal Huntington's disease: A marker of disease onset?

2012 ◽  
Vol 50 (14) ◽  
pp. 3273-3278 ◽  
Author(s):  
Adam P. Vogel ◽  
Christopher Shirbin ◽  
Andrew J. Churchyard ◽  
Julie C. Stout
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Early Stage ◽  
Disease Onset

scholarly journals Differential Diagnosis of Chorea—HIV Infection Delays Diagnosis of Huntington’s Disease by Years

2021 ◽  
Vol 11 (6) ◽  
pp. 710
Author(s):  
Jannis Achenbach ◽  
Simon Faissner ◽  
Carsten Saft
Keyword(s):  
Hiv Infection ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Onset ◽  
Diagnostic Delay ◽  
Depression Scale ◽  
Cag Repeat ◽  
Psychiatric Disease ◽  
Disease Manifestation ◽  
Cross Sectional

Background: There is a broad range of potential differential diagnoses for chorea. Besides rare, inherited neurodegenerative diseases such as Huntington’s disease (HD) chorea can accompany basal ganglia disorders due to vasculitis or infections, e.g., with the human immunodeficiency virus (HIV). The clinical picture is complicated by the rare occurrence of HIV infection and HD. Methods: First, we present a case suffering simultaneously from HIV and HD (HIV/HD) focusing on clinical manifestation and disease onset. We investigated cross-sectional data regarding molecular genetic, motoric, cognitive, functional, and psychiatric disease manifestation of HIV/HD in comparison to motor-manifest HD patients without HIV infection (nonHIV/HD) in the largest cohort of HD patients worldwide using the registry study ENROLL-HD. Data were analyzed using ANCOVA analyses controlling for covariates of age and CAG repeat length between groups in IBM SPSS Statistics V.25. Results: The HD diagnosis in our case report was delayed by approximately nine years due to the false assumption that the HIV infection might have been the cause of chorea. Out of n = 21,116 participants in ENROLL-HD, we identified n = 10,125 motor-manifest HD patients. n = 23 male participants were classified as suffering from HIV infection as a comorbidity, compared to n = 4898 male non-HIV/HD patients. Except for age, with HIV/HD being significantly younger (p < 0.050), we observed no group differences regarding sociodemographic, genetic, educational, motoric, functional, and cognitive parameters. Male HIV/HD patients reported about a 5.3-year-earlier onset of HD symptoms noticed by themselves compared to non-HIV/HD (p < 0.050). Moreover, patients in the HIV/HD group had a longer diagnostic delay of 1.8 years between onset of symptoms and HD diagnosis and a longer time regarding assessment of first symptoms by the rater and judgement of the patient (all p < 0.050). Unexpectedly, HIV/HD patients showed less irritability in the Hospital Anxiety and Depression Scale (all p < 0.05). Conclusions: The HD diagnosis in HIV-infected male patients is secured with a diagnostic delay between first symptoms noticed by the patient and final diagnosis. Treating physicians therefore should be sensitized to think of potential alternative diagnoses in HIV-infected patients also afflicted by movement disorders, especially if there is evidence of subcortical atrophy and a history of hyperkinesia, even without a clear HD-family history. Those patients should be transferred for early genetic testing to avoid further unnecessary diagnostics and improve sociomedical care.

Plasma inflammatory biomarkers for Huntington’s disease patients and mouse model

2015 ◽  
Vol 44 ◽  
pp. 121-127 ◽  
Author(s):  
Kuo-Hsuan Chang ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Chiung-Mei Chen
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Inflammatory Biomarkers
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