Journal of Huntington's disease最新文献

{"title":"Mitochondrial dynamics in Huntington's disease.","authors":"Beatriz Paiva, Ana Cristina Rego","doi":"10.1177/18796397261478163","DOIUrl":"https://doi.org/10.1177/18796397261478163","url":null,"abstract":"<p><p>Emerging evidence suggests a central and early role of mitochondrial dysfunction, including altered mitochondrial dynamics, in Huntington's disease (HD) pathogenesis. Processes such as mitochondrial fission, fusion, transport and mitophagy are vital for proper mitochondrial function and seem to be key mediators of neuronal vulnerability in HD. In this review, we summarize mechanistic insights into mitochondrial dynamics in HD, highlighting how mutant huntingtin (mHTT) impairs mitochondrial biogenesis and morphology, disrupts Drp1-dependent fission, compromises fusion, transport and organelle crosstalk with the endoplasmic reticulum, and disrupts mitochondrial quality control, ultimately leading to neuronal degeneration. Since these alterations correlate with bioenergetic deficits, calcium dysregulation and oxidative stress, we highlight how altered mitochondrial dynamics contribute to and possibly drive HD pathogenesis. Furthermore, we discuss how mitochondrial dynamics in HD can be altered based on cell type specificity, experimental model and disease stage.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261478163"},"PeriodicalIF":2.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759391","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":"Real-world treatment patterns and outcomes of deutetrabenazine in patients with chorea associated with Huntington disease: A retrospective chart review study.","authors":"Victor Sung, Ashley White, Hela Romdhani, Sakshi Sethi, Debbie Goldschmidt, Rajeev Ayyagari, Nayla Chaijale, Ayelet Yaari, Mark Forrest Gordon, Amy Yang, Rinat Ribalov","doi":"10.1177/18796397261468475","DOIUrl":"https://doi.org/10.1177/18796397261468475","url":null,"abstract":"<p><p>IntroductionReal-world evidence of deutetrabenazine (DTBZ) treatment for Huntington disease (HD)-associated chorea is limited.MethodsThis is a non-interventional, retrospective chart review study from a Huntington's Disease Society of America clinical practice at the University of Alabama at Birmingham (UAB). Patients had a diagnosis of HD-associated chorea, DTBZ initiation (4/2017-12/2021), ≥2 visits at UAB, and ≥3 months of chorea-related care records post DTBZ initiation. The last Unified HD Rating Scale-Total Maximal Chorea (TMC) score within 3 months prior to DTBZ initiation and first after reaching the last stable dose during follow-up were analyzed.ResultsAmong 80 eligible patient charts, mean (SD) age was 52.1 (12.6) years and 45 (56.3%) were female. Fifty patients had pre- and post-DTBZ TMC scores and reached a stable dose, including 30 with no prior tetrabenazine (TBZ) or DTBZ exposure, 8 with prior TBZ exposure with a switch to DTBZ after a gap, and 9 with prior TBZ exposure with a switch to DTBZ without a gap. Mean (SD) TMC score decreased (i.e., improved) by 3.7 (4.5), 7.8 (2.8), and 2.1 (4.2), respectively. Overall, 27 (33.8%) patients had ≥1 adverse event recorded between DTBZ initiation and the first visit with a TMC score after reaching their last stable DTBZ dose or DTBZ discontinuation for those without a stable dose.DiscussionThis real-world study describes improvements in TMC scores among patients with HD-associated chorea treated with DTBZ, regardless of prior treatment. The observed safety profile supports the known safety profile of DTBZ in this population.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261468475"},"PeriodicalIF":2.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764742","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":"Altered myelin sphingolipid and glycerophospholipid profiles in Huntington disease.","authors":"Michael G Friedrich, Gabrielle R Phillips, Reuben Se Young, Sarah Cameron, Luke K Bale, Jesse A Michael, Huaqi Su, Helena Targa Dias Anastacio, Catriona A McLean, Gavin E Reid, Todd W Mitchell","doi":"10.1177/18796397261472539","DOIUrl":"https://doi.org/10.1177/18796397261472539","url":null,"abstract":"<p><p>Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin gene (<i>HTT</i>). While classically considered a disease of grey matter, recent imaging data have revealed presymptomatic abnormalities in white matter (WM) tracts. Here, we report lipid changes in glycerophospholipids and sphingolipids from enriched myelin extracts of three WM tracts (internal capsule (IC), dorsomedial prefrontal cortex (dmPFC), corpus callosum (CC)) of HD and control donors. We found no difference in total lipid concentration between HD and control myelin. However, changes were observed at the lipid class level for the CC and dmPFC, with a reduction in the proportion of Hexosylceramides in HD myelin. When lipids were examined at a species level, there was a shift towards shorter glycerophospholipid fatty acid chain length in HD for all three regions, most notably in phosphatidylethanolamine species. This coincides with previous data showing a reduction in fatty acyl chain lengths in sphingolipid species in the caudate of the same donor cohort and suggests a widespread impact of HD on fatty acid metabolism in the brain.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261472539"},"PeriodicalIF":2.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701382","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":"Experiences and perceptions of affected individuals, families, caregivers and healthcare professionals regarding end-of-life planning in Huntington's disease: A narrative synthesis.","authors":"Catherine Lyon, Chris Williams, Suzanne Buswell, Selina Lock, Sarah Gunn","doi":"10.1177/18796397261428341","DOIUrl":"10.1177/18796397261428341","url":null,"abstract":"<p><p>IntroductionPeople with Huntington's disease (HD) are encouraged to consider end-of-life planning early on to mitigate future challenges. Initial evidence shows that undertaking planning discussions around this subject presents various barriers; however, a comprehensive evidence synthesis has not been completed to date. Accordingly, we here synthesise evidence regarding experiences of end-of-life planning discussions (EOLPD) among people with HD, their families and familial caregivers, and healthcare professionals supporting them.MethodsFive databases were systematically searched for peer-reviewed articles addressing the research question. After screening, eight articles meeting the inclusion criteria were identified, and a narrative synthesis undertaken to develop key themes.ResultsFour themes were developed. \"The value of EOLPD\" details the perceived effectiveness of such discussions. \"To talk or not to talk\" reflect motivations to seek out or avoid EOLPD. \"A clear vision of the future\" encapsulates how EOLPD may provide comfort for some but fear and anxiety for others. The final theme highlights the importance of those engaging in EOLPD accessing \"The right people at the right time\".DiscussionEnd-of-life planning in HD remains inconsistently implemented and often process-focused, with a need for more holistic and patient-centred discussions. Further research is necessary to explore needs, expectations and experiences among HD families, and to support healthcare professionals to successfully lead on introducing these discussions. Additionally, much of the literature addressed euthanasia rather than natural death, highlighting a need for more research in the context of natural death.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"317-331"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463364","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":"A moderate-intensity exercise program during inpatient rehabilitation for middle stage Huntington's disease: A randomized controlled trial.","authors":"Mathis Brusseau, Brigitte Soudrie, Anne-Catherine Bachoud-Lévi, Stéphanie Bannier, Frédéric Bourdain, Marine Jenkins, Pierre-André Natella, Nolwenn Bombenger, Julie Boiché","doi":"10.1177/18796397261422975","DOIUrl":"10.1177/18796397261422975","url":null,"abstract":"<p><p>BackgroundExercise is beneficial for persons with Huntington's disease (HD). Inpatient rehabilitation settings are well-suited for implementing exercise programs. Exercise parameters, such as duration and intensity, need to be further investigated. The objective of our study was to evaluate the effects of an exercise program at moderate intensity performed five times a week for persons with mid-stage HD during a four-week inpatient rehabilitation program.MethodsIn a single-blind randomized monocentric controlled trial, two groups followed a four-week inpatient rehabilitation program including: occupational therapy, psychomotor therapy, psychosocial workshop, mobility sessions, dietary management, nursing, socio-educational activities, physician consultations and personalized consultations. In addition, the intervention group specifically participated in five one-hour exercise sessions per week at moderate intensity (flat ground walking, sand walking, resistance training, adaptive cycling and water activities), whereas the control group engaged in specific activities without physical activity. The primary outcome was the UHDRS-modified Motor Score (mMS). Functional, cognitive and psychological assessments were also completed.ResultsThirty-two patients were recruited. The UHDRS-mMS did not significantly differ at post-intervention. In the intervention group (n = 16), within-group improvements were observed for HAD-Anxiety, PBA-apathy, PBA-depression, PBA-psychosis; both within and between-group for 6-min walk test, Stroop Word Reading, and PBA-executive function; and between-group only for Borg. The control group (n = 16) improved within-group on PBA components: depression, apathy and irritability.ConclusionsInpatient rehabilitation program had positive effects on psychological symptoms, while exercise produced additional positive effects beyond exercise tolerance, anxiety, STROOP Word Reading and executive function. Inpatient rehabilitation programs may require longer-term post-rehabilitation support.Trial registrationNCT04917133.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"453-467"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do young carriers of Huntington's disease mature earlier?","authors":"Simon Okholm","doi":"10.1177/18796397261443433","DOIUrl":"https://doi.org/10.1177/18796397261443433","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"15 3","pages":"538-539"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562066","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":"TRACE: Open-source software for quantifying somatic variation of tandem repeats by capillary electrophoresis.","authors":"Andrew Jiang, Kevin Correia, Tammy Gillis, Esaria L Oliver, Benjamin P Jones, Branduff McAllister, Alan Mejia Maza, Marcy E MacDonald, Ricardo Mouro Pinto, Vanessa C Wheeler, James F Gusella, Zachariah L McLean","doi":"10.1177/18796397261448958","DOIUrl":"10.1177/18796397261448958","url":null,"abstract":"<p><p>Expanded short tandem DNA repeats are implicated in over 60 human disorders. In many, somatic instability (SI) of the repeat plays a critical role in disease pathogenesis. For example, SI in vulnerable neurons is a key driver of clinical symptoms in Huntington's disease. Quantifying SI has traditionally relied on PCR followed by capillary electrophoresis, with metrics describing the shape of repeat size distributions, such as the expansion index. However, current tools often require costly proprietary software, are time-consuming, and rely on custom pipelines that vary between labs. To address these challenges, we developed Tandem Repeats Analysis by Capillary Electrophoresis (TRACE), an open-source software that processes fragment analysis data end-to-end, from raw files to SI metrics. Additionally, we created an associated web app TRACE-shiny (https://traceshiny.mgh.harvard.edu), for interactive usage. Instability metrics from TRACE benchmarked against published datasets confirm its utility for studying genetic and pharmacological modifiers of SI. TRACE eliminates the need for proprietary software or custom pipelines, making advanced tools for analysis of somatic repeat expansion widely accessible.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"506-515"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current knowledge of Huntington's disease-like 2 genetic testing, clinical presentation, and patient experiences: A systematic review.","authors":"Katharina Hoffmann, Stephanie White, Adrienne Sexton","doi":"10.1177/18796397251411109","DOIUrl":"10.1177/18796397251411109","url":null,"abstract":"<p><p>BackgroundHuntington's Disease-like 2 (HDL2) presents complexities in diagnosis due to its similarity to Huntington's Disease (HD). Limited research highlights gaps in knowledge about management and genetic counselling for the condition. HDL2 is rare but an important differential diagnosis for individuals with HD-like symptoms who have tested negative for HD.ObjectiveThis review aimed to synthesise published clinical and genetic data on HDL2, identify knowledge gaps, and serve as a resource for healthcare professionals supporting individuals affected by or at risk of HDL2.MethodsA mixed method integrative systematic review of four databases (Medline, Embase, Scopus, and PsycINFO) generated 323 peer-reviewed articles, of which 36 were included. Data about clinical features, genetic testing and counselling, and patient experiences were interpreted via narrative synthesis.ResultsThe majority of included studies explored the clinical features, genetic testing results and medical histories of individuals with HDL2. A total of 109 people with HDL2 were reported. Limited data was obtained about genetic counselling, management and support, and experiences of those with HDL2 and their families. Findings related to seven categories: DNA repeat length and impact on phenotype, age of onset and disease duration, family history, African ancestry, neurological characteristics, clinical characteristics, and experiences and support.ConclusionsThis review highlights the importance of understanding the reduced penetrance range and early psychiatric symptoms in HDL2 for accurate genetic counselling and interpretation of test results. Adapting existing protocols for HD and qualitatively collecting patient experiences can inform the development of a HDL2 genetic testing and counselling protocol.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"293-316"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of human <i>HTT</i> by targeted CRISPR/dCas9-mediated epigenetic editing.","authors":"Yi Lin Tay, Sarah B Thomson, Silvia Hnatova, Sherwin Ng, Si Rui Teo, Ryan McCallum, Bernice Sim, Letizia Tarantini, Fei Li Tai, Valentina Bollati, Marie Loh, Michael R Hayden, Blair R Leavitt, Mahmoud A Pouladi","doi":"10.1177/18796397251415368","DOIUrl":"10.1177/18796397251415368","url":null,"abstract":"<p><p>BackgroundGene silencing is widely recognized as a promising therapeutic approach for dominant monogenic disorders. Current silencing strategies, many of which are transient, utilize RNA interference. Gene silencing may also be achieved through directed epigenetic editing using a CRISPR/dCas9 effector fused to DNA methyltransferase 3A (dCas9-DNMT3A). We used this system to direct DNA methylation to <i>HTT</i>, the causal gene underlying the autosomal dominant neurodegenerative disorder Huntington's disease, to assess the translational potential of this strategy for treating a genetic neurological disease.ObjectiveTo characterize the regulatory effect of targeted dCas9-DNMT3A-mediated DNA methylation at <i>HTT</i>.MethodsWe exploited DNA methylation profiles of high and low <i>HTT</i>-expressing tissues and targeted hypomethylated regions of <i>HTT</i> associated with high levels of <i>HTT</i> expression.Results<i>De novo</i> DNA methylation of loci within defined upstream, promoter, intragenic and downstream regions of <i>HTT</i> resulted in robust, acute silencing of <i>HTT</i>. The best long-term silencing of <i>HTT</i>, which persisted up to 30 days, was observed when targeted DNA methylation was directed to the 5'UTR and promoter regions of <i>HTT</i>.Conclusions<i>HTT</i> gene silencing may be achieved via targeted <i>de novo</i> DNA methylation within hypomethylated regulatory regions at the <i>HTT</i> locus. DNA methylation editing may be an attractive therapeutic approach for Huntington disease due to its potential for long-term silencing and reversibility.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"399-407"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring quality of care through the eyes of formal and informal caregivers for residents with Huntington's disease: A qualitative descriptive study.","authors":"Joyce Cf Heffels, Irma Hj Everink, Raymund Ac Roos, Jos Mga Schols, Mayke Oosterloo","doi":"10.1177/18796397251410253","DOIUrl":"10.1177/18796397251410253","url":null,"abstract":"<p><p>AimTo gain insight into factors contributing to the quality of care in nursing homes specialized in Huntington's disease from the perspectives of formal and informal caregivers.DesignA qualitative descriptive focus group study.MethodsFormal and informal caregivers from three specialized nursing homes in the Netherlands were separated into six focus groups. All data was analyzed using reflexive thematic analysis.ResultsFrom both groups, three main themes were explored: (1) care approaches and principles, (2) attention to specific care domains, and (3) preconditions for delivering care. Formal caregivers highlighted the importance of balancing residents' autonomy and restrictions, the need to work systematically, and adopting a resident-centered approach. Furthermore, attention to palliative care, nutritional care, and emotional support are needed. Informal caregivers emphasized the need for providing structure, supportive conversations, and the importance of the nursing home environment itself. Attention to the transition phase immediately after admission to the nursing home, as well as guidance on future care planning, is important. There is a need for care teams that consist of knowledgeable, familiar caregivers within a care organization that (im)materially supports its staff.ConclusionMaintaining autonomy despite disease-related restrictions, providing structure, applying palliative care principles, and offering emotional support are essential components of quality of care, as emphasized by both formal and informal caregivers. Achieving this requires systematic nursing practices performed by a team of knowledgeable caregivers. Although informal caregivers' descriptions are more superficial, key elements in them are similar to those of formal caregivers.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"439-452"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}