Journal of Huntington's disease最新文献

{"title":"Letter in response to Fuller et al., Functional Rating Scale 2.0 (FuRST 2.0): A patient-reported outcome measure of function for Huntington's disease.","authors":"Brett L Kinsler, Chad Heatwole","doi":"10.1177/18796397251376458","DOIUrl":"https://doi.org/10.1177/18796397251376458","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251376458"},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.","authors":"Christina Peng, Tamara Maiuri, Ray Truant","doi":"10.1177/18796397251372667","DOIUrl":"https://doi.org/10.1177/18796397251372667","url":null,"abstract":"<p><p>Poly(ADP-ribosyl)ation (PARylation), a crucial post-translational modification, is catalyzed by ADP-ribosyltransferases (ARTs) and has significant implications in various cellular processes, including DNA damage response, cell signaling, and immune processes. Aberrant PAR signaling is implicated in numerous neurodegenerative diseases, including Alzheimer, Parkinson, amyotrophic lateral sclerosis, and cerebellar ataxia, where increased PAR levels and PARP1 activity are commonly observed. However, Huntington disease exhibits a unique characteristic: reduced PAR levels and impaired PARP1 activity even in prodromal phase. This finding challenges the prevailing understanding of PAR's role in neurodegeneration and suggests that dysregulation of PAR signaling, whether through overactivation or suppression, can lead to neuronal dysfunction. Herein, we discuss how this balance may impact neurodegenerative diseases, and possible connections between PAR signaling and emerging modifiers of disease onset identified by HD genome-wide association studies (GWAS).</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251372667"},"PeriodicalIF":3.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the relationship between patient-reported outcome measures, clinician-rated assessments, and performance-based measures (cognitive tests and device-based estimates) of symptoms and functioning in people with Huntington's disease.","authors":"Noelle E Carlozzi, Jonathan P Troost, Wendy L Lombard, Jennifer A Miner, Praveen Dayalu","doi":"10.1177/18796397251366313","DOIUrl":"https://doi.org/10.1177/18796397251366313","url":null,"abstract":"<p><p>BackgroundGiven the progressive cognitive decline in Huntington's disease (HD), most research in this population relies solely on objective assessments of symptoms and function, rather than on patient-reported outcome (PRO) measures.ObjectiveThe purpose of this paper is to understand how PRO measures relate to clinician-rated assessments and performance-based measures (cognitive tests and device-based estimates) of symptoms and functioning in people with HD.MethodsWe enrolled N = 52 participants with HD in this study. Participants completed several self-reported PROs as well as clinician-administered assessments and performance-based measures (cognitive tests and device-based estimates) of related concepts. Pearson correlations and linear regression models were used to examine the concordance among PROs, clinician-rated assessments, and performance-based measures.ResultsThere were strong relationships among PROs that assessed related concepts. There were also strong relationships between PROs and associated clinician-rated assessments of physical functioning (chorea, sleep/fatigue) and mental health, and slightly less robust relationships between the PROs and associated clinician-rated assessments for speech/swallowing and cognition. Relationships between PROs and associated performance-based measures were moderate for chorea/motor functioning, but negligible for sleep/fatigue and cognition.ConclusionsFindings from this study support the construct validity of PROs that assess motor functioning and mental health among individuals with HD and indicate that PROs and clinician-rated assessments of these constructs (i.e., motor functioning and mental health) provide complementary information. On the other hand, the negligible relationships between PROs and associated performance-based cognitive tests and between PROs and associated wearable device-based estimates of sleep and physical activity indicate that reliance solely on HD patients' self-report for these concepts might be misleading.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251366313"},"PeriodicalIF":3.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal neurodevelopment predisposes to cortical hyperexcitability in Huntington's disease.","authors":"Carlos Cepeda, Joshua Barry, Sandra M Holley","doi":"10.1177/18796397251366891","DOIUrl":"10.1177/18796397251366891","url":null,"abstract":"<p><p>Accumulating morphological and electrophysiological evidence demonstrates that abnormal brain development is a key element in the progression of Huntington's disease (HD). Mutant huntingtin affects corticogenesis, cell migration, and differentiation. Cortical changes are reminiscent of focal cortical dysplasia, a malformation of cortical development that leads to hyperexcitability and epilepsy. Striatal development also is affected by the mutation. In animal models, recent studies provide additional evidence that neuronal morphology and intrinsic and electrophysiological properties deviate from normal development. Some changes indicate delayed development of cortical pyramidal neurons, while a subtype of striatal projection neuron displays a transient accelerated maturation. However, the brain is able to compensate for early abnormalities and, during a variable latent period, brain function appears normal. Eventually, homeostatic mechanisms begin to fail, resulting in the emergence of HD symptoms. The realization that neurodevelopment in HD is abnormal offers new insights and opens new avenues for early treatment. In this review, we present a brief summary of imaging and morphological studies from human carriers of the HD mutation followed by a more in-depth examination of recent findings in genetic animal models.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251366891"},"PeriodicalIF":3.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bias in HD-ISS staging introduced by the FreeSurfer cross-sectional stream: Insights from the Huntington's Disease Young Adult Study (HD-YAS).","authors":"Harry Knights, Annabelle Coleman, Mena Farag, Michela Leocadi, Michael Murphy, Kate Fayer, Olivia Thackeray, Douglas Langbehn, Nicola Hobbs, Sarah J Tabrizi, Rachael I Scahill","doi":"10.1177/18796397251366900","DOIUrl":"https://doi.org/10.1177/18796397251366900","url":null,"abstract":"<p><p>Huntington's Disease Integrated Staging System (HD-ISS) stages are likely inclusion criteria in future clinical trials. Stage 1 volumetric cut-offs were derived using the FreeSurfer longitudinal stream (LG). However, trials will require cross-sectional stream (CS) application with one MRI. Volumetric outputs are not robust to software type or version. T1-weighted images from 88 participants with MRIs from baseline and follow-up HD-YAS visits were segmented using both streams. CS calculated smaller caudate and putamen volumes adjusted for total intracranial volume, with greater reduction for larger volumes, shifting towards HD-ISS stage 1. CS-specific cut-offs need to be established before application to clinical trials.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251366900"},"PeriodicalIF":3.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of cholinesterase inhibitors and memantine for cognitive symptoms in patients with Huntington's disease: A systematic review.","authors":"Catarina Correia Rodrigues, Vanessa Carvalho, Filipa Dourado Sotero, Eoin Mulroy, Leonor Correia Guedes","doi":"10.1177/18796397251367689","DOIUrl":"https://doi.org/10.1177/18796397251367689","url":null,"abstract":"<p><p>BackgroundHuntington's Disease (HD) is an autosomal dominant neurodegenerative disorder. Clinical features encompass a broad spectrum of movement disorders, psychiatric and cognitive symptoms, often progressing to dementia and imposing a substantial burden on patients and their families. While cholinesterase inhibitors and memantine are often used for symptomatic treatment of Alzheimer's Disease and other dementias, there is currently no approved medication for treating cognitive symptoms in HD.ObjectiveWe aim to review, summarize, and appraise evidence from the literature for the use of cholinesterase inhibitors and memantine in the treatment of cognitive symptoms in patients with HD.MethodsA searched was conducted in PubMed and SCOPUS, from inception until February 2024, for Randomized Clinical Trials (RCTs), open-label, and case-control studies. Quality appraisal was performed using ROBINS-I and ROB2 for non-randomized studies and RCTs, respectively.ResultsFive eligible studies (three RCTs, one extension study, and one retrospective case-control), exploring the use of rivastigmine (n = 3), memantine (n = 1), and donepezil (n = 1) were found. Only two had a follow-up period longer than eight months. Previous cognitive functioning was not specified in three out of five studies. Cognitive measures varied widely, with Unified Huntington's Disease Rating Scale and Mini-Mental State Exam being used more frequently. None of the studies showed a significant improvement in cognitive function. Side effects occurred in up to 50% of patients and were usually considered mild.ConclusionsThere is insufficient evidence in the literature to support the use of cholinesterase inhibitors or memantine for cognitive symptoms in patients with HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251367689"},"PeriodicalIF":3.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of astrocytes in human Huntington's disease pathology.","authors":"Osama Al-Dalahmah, James E Goldman","doi":"10.1177/18796397251344173","DOIUrl":"https://doi.org/10.1177/18796397251344173","url":null,"abstract":"<p><p>Huntington's disease (HD) is a neurodegenerative disorder caused by a repeat expansion in the <i>HTT</i> gene. The disease is well known for severe and progressive loss of neurons in the caudate and putamen, although other areas are also involved. Much of the attention on understanding the mechanisms underlying HD has focused on the neurons. The brain also contains large numbers of glial cells, such as astrocytes, oligodendrocytes, and microglia, which also become dysfunctional in HD. Astrocytes are one of the most abundant cell types in the central nervous system and are critical for regulating the brain environment and supporting neurons in many ways. In this review, we discuss the changes in astrocytes during the evolution of HD in the human brain. We detail the key phenotypes of astrocytes in human HD, which encompass reactive astrogliosis, loss of homeostatic function, gain of a neuroprotective function, changes in lipid metabolism, huntingtin protein aggregation, and limited somatic repeat expansion. We briefly discuss the conservation of these phenotypes in mouse models and propose a model of how astrocyte states change in human HD. Finally, we present open questions for astrocyte researchers in the HD field. Together, this review represents a valuable resource for readers interested in astrocytic changes in human HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"14 3","pages":"214-228"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface by the Editors-in-Chief.","authors":"Blair R Leavitt, Leslie M Thompson","doi":"10.1177/18796397251363441","DOIUrl":"10.1177/18796397251363441","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"14 3","pages":"211"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface by the Editors-in-Chief.","authors":"Blair R Leavitt, Leslie M Thompson","doi":"10.1177/18796397251363441","DOIUrl":"https://doi.org/10.1177/18796397251363441","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"14 3","pages":"211"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special issue: Glia and non-neuronal cells in Huntington's disease.","authors":"Mahmoud A Pouladi, Asa Petersen","doi":"10.1177/18796397251358289","DOIUrl":"https://doi.org/10.1177/18796397251358289","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"14 3","pages":"212-213"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}