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Introduction: Huntington's disease (HD) is a neurodegenerative autosomal dominant disorder affecting patients' motor, behavioral and cognitive domains leading to total dependency for activities of daily life. This study compares whether gender differences in motor, cognitive and behavioral symptoms affect function and how functional impairment affects quality of life (QoL).Methods: We recruited 2191 subjects from the REGISTRY data base that provides personal data, HD age of onset, visit date, CAG mutation size, UHDRS and TFC scores from at least one visit. For 1166 participants SF-36 was also available. We calculated Spearman coefficients for correlations between particular symptomatic domains and functional scales, Fisher z-transform was used to test whether differences in correlations between genders were statistically significant. Simultaneous linear regression with least-square fit method was used to determine for how much variability in functional scales the particular symptomatic domains are responsible. ANOVA was used to look for QoL differences between TFC-stage based groups. Baseline statistics showed no significant differences between genders.Results: Motor, cognitive and behavioral domains contributed significantly to function and independence. The motor domain contributed most followed by the cognitive and to a lesser degree by the behavioral domain. Motor symptoms correlated more with functional ability and influenced function variability more in women than in men. The decline in functional abilities correlated significantly with QoL decline.Conclusion: Motor symptoms have highest impact on function in HD, moreover these symptoms affect female function and independence more than males. Results indicate that symptomatic treatment targeting motor symptoms is needed to improve HD function and QoL. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is mainly thought of as a neurological disease, but multiple epidemiological studies have demonstrated a number of cardiovascular events leading to heart failure in HD patients. Our recent studies showed an increased risk of heart contractile dysfunction and dilated cardiomyopathy in HD pre-clinical models. This could potentially involve metabolic remodeling, that is a typical feature of the failing heart, with reduced activities of high energy phosphate generating pathways. In this study, we sought to identify metabolic abnormalities leading to HD-related cardiomyopathy in pre-clinical and clinical settings. We found that HD mouse models developed a profound deterioration in cardiac energy equilibrium, despite AMP-activated protein kinase hyperphosphorylation. This was accompanied by a reduced glucose usage and a significant deregulation of genes involved in de novo purine biosynthesis, in conversion of adenine nucleotides, and in adenosine metabolism. Consequently, we observed increased levels of nucleotide catabolites such as inosine, hypoxanthine, xanthine and uric acid, in murine and human HD serum. These effects may be caused locally by mutant HTT, via gain or loss of function effects, or distally by a lack of trophic signals from central nerve stimulation. Either may lead to energy equilibrium imbalances in cardiac cells, with activation of nucleotide catabolism plus an inhibition of re-synthesis. Our study suggests that future therapies should target cardiac mitochondrial dysfunction to ameliorate energetic dysfunction. Importantly, we describe the first set of biomarkers related to heart and skeletal muscle dysfunction in both pre-clinical and clinical HD settings. [ABSTRACT FROM AUTHOR]

Introduction Huntington's disease (HD) is the most common hereditary neurodegenerative disorder. Despite the fact that both the gene and the mutation causing this monogenetic disorder were identified more than 20 years ago, disease-modifying therapies for HD have not yet been established. Review While intense preclinical research and large cohort studies in HD have laid foundations for tangible improvements in understanding HD and caring for HD patients, identifying targets for therapeutic interventions and developing novel therapeutic modalities (new chemical entities and advanced therapies using DNA and RNA molecules as therapeutic agents) continues to be an ongoing process. The authors review recent achievements in HD research and focus on approaches towards disease-modifying therapies, ranging from huntingtin-lowering strategies to improving huntingtin clearance that may be promoted by posttranslational HTT modifications. Conclusion The nature and number of upcoming clinical studies/trials in HD is a reason for hope for HD patients and their families. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Huntington''s disease (HD) is an autosomal dominant neurodegenerative disorder. The aim of this study is to determine whether gender plays a role in the phenotypic expression and progression of HD. Methods: 1267 patients with HD (636 women) from the Registry project of the EHDN were included. A cross-sectional analysis (ANCOVA) controlling for differences in age at onset, disease burden, disease duration, smoking status, alcohol abuse, depression and the number of years of education, was performed to evaluate if there were differences between men and women in UHDRS motor, function and cognitive scores. Additionally, analyses on follow-up data using linear mixed models with the same covariates were performed to test for gender-related differences in progression. Results: Baseline features did not differ between genders, with the exception of a higher frequency of past and current depression among women, and a higher number of years of education as well as more frequent alcohol abuse and smoking among men. In the cross-sectional ANCOVA analyses of patients with a mid-age HD onset, women showed worse scores than men in the functional domain (TFC, P = 0.001; UHDRS functional, P = 0.033), UHDRS motor (P = 0.033). The longitudinal analyses showed a faster rate of progression in women in the functional assessment (P = 0.025), the motor assessment (P = 0.032) and the independence scale (P = 0.008). Conclusions: These results suggest a complex gender effect on the phenotypical presentation and the rate of disease progression in HD, with slightly more severe phenotype and faster rate of progression in women in especially the motor and functional domains. [Copyright &y& Elsevier]