Journal of Huntington's disease最新文献

{"title":"Clinical implications of loss of interruption variants for diagnosis, genetic counselling, and clinical trials in Huntington's disease.","authors":"Hailey Findlay Black, Jessica Levesley, Chris Kay, Stephanie Bortnick, Kyla Javier, Michael R Hayden","doi":"10.1177/18796397261443135","DOIUrl":"10.1177/18796397261443135","url":null,"abstract":"<p><p>Age of onset in Huntington disease (HD) is influenced by <i>cis-</i>acting genetic variants, particularly the loss of interrupting codons in the <i>HTT</i> CAG and CCG repeats (CAG-CCG LOI variant). The CAG-CCG LOI variant is not detectable by current diagnostic assays, leading to underestimation of CAG repeat length, misdiagnosis, and inaccurate prediction of risk of symptom onset in the reduced penetrance range. In clinical trials, unidentified CAG-CCG LOI variants may affect interpretation of results, particularly for small trials. Accurate ascertainment and reporting of the CAG-CCG LOI genotype therefore has important implications for HD diagnosis, genetic counselling, and clinical trial design.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"516-523"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042437","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":"The girl at the end of the world - a reflection on humanitarian and care work in Barranquitas, Venezuela.","authors":"Alex Fisher","doi":"10.1177/18796397261416568","DOIUrl":"10.1177/18796397261416568","url":null,"abstract":"<p><p>This piece recounts the deeply personal journey of the author (Alex) in supporting families affected by Huntington's Disease (HD) in Barranquitas, Venezuela. The author draws a parallel between her childhood fascination with small spaces and the overlooked potential for innovation within small communities, especially Barranquitas, which played a pivotal part in the HD genetics research led by Dr Nancy Wexler in the 1980s and 1990s. The narrative details Alex's involvement with Factor-H and Habitat Luz, NGOs dedicated to aiding HD families in Latin America by providing essential resources, health support, and caregiver assistance amidst political and economic turmoil. The story highlights the challenges faced by the communities, and the emotional impact for Alex of witnessing extreme neglect. It describes Alex's leadership in establishing the Caregivers' Programme and pursuing imaginative solutions, such as a roving caregiving team, an innovation that was recognized by the prestigious Amgen Prize for Rare Diseases. The author underscores the ongoing commitment of Factor-H and Habitat Luz to improving lives in a community where state support is minimal and caregiving often remains an invisible but vital responsibility that we all have in the era of therapeutic advancement.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"289-292"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989611","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 holistic burden of Huntington's disease: A qualitative study of multigenerational impact on individuals and family caregivers across Europe.","authors":"Charlie Albert Smith, Savita Bakhshi Anand, Astri Arnesen, Cecilia Jimenez-Moreno, Charles Patrick Khoury, Helen Luck, Joshua Trivlidis, Doorsa Tarazi, Mai-Lise Nguyen, Anna Kotzeva, Kunal Samanta, Carla Dias Barbosa","doi":"10.1177/18796397261443133","DOIUrl":"10.1177/18796397261443133","url":null,"abstract":"<p><p>Huntington's disease (HD) is a progressive, inherited neurodegenerative condition that imposes a profound, multidimensional burden on individuals with HD and their families. This qualitative study explored the physical, emotional, socioeconomic, and intergenerational impact of HD across six European countries, drawing on interviews with individuals diagnosed with HD and family caregivers. Findings reveal that HD disrupts daily functioning, employment, relationships, and long-term planning. Cognitive and psychiatric symptoms were particularly burdensome, driving declines in quality of life (QoL) and emotional well-being. Caregivers reported extensive physical, financial, and psychological strain, with many assuming care responsibilities from a young age or eventually caring for multiple relatives. These burdens frequently spanned generations, with participants describing how HD shaped their upbringing, reproductive choices, and expectations for future caregiving.Despite some optimism regarding future research, participants expressed concern that therapeutic advances would not arrive in time to benefit them, reinforcing the urgency for non-pharmacological support. There was strong support for more accessible, consistent, and family-centred care models that integrate clinical services with psychosocial and financial supports. Participants emphasized the importance of early diagnosis, proactive care planning, and coordinated support networks to mitigate caregiver burden and improve long-term outcomes.These findings underscore the need for healthcare systems and policies to move beyond symptom management and address HD as a multigenerational, systemic challenge which needs to be met with a holistic model of care responsive to the evolving needs of both patients and caregivers.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"487-505"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982127","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":"Psychosis in Huntington's disease: A case supporting multidisciplinary and early palliative care.","authors":"Vy Le, Edith Sigler, Jonathan Liu, Hiba Abualama, Kamalakar Surineni","doi":"10.1177/18796397261472525","DOIUrl":"https://doi.org/10.1177/18796397261472525","url":null,"abstract":"<p><p>Following an abrupt medication switch from olanzapine to aripiprazole, a 61-year-old female with Huntington's disease developed psychosis that persisted despite olanzapine reinstitution. Subsequent hospitalization led to significant complications, including medication adverse effects, infections (parotitis, endocarditis, cystitis), trauma in the setting of restraints, and malnutrition. This case illustrates the risk of medical and pharmacologic complications during prolonged hospitalization, diagnostic challenges in advanced HD, and the importance of multidisciplinary care with early palliative involvement.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261472525"},"PeriodicalIF":2.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603824","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":"Prevention of appearance of severe Huntington's disease symptoms in the R6/1 mouse model by early administration of 4',5,7-trihydroxyisoflavone.","authors":"Lidia Gaffke, Estera Rintz, Magdalena Podlacha, Dorota Myślińska, Grzegorz Węgrzyn, Karolina Pierzynowska","doi":"10.1177/18796397261472379","DOIUrl":"https://doi.org/10.1177/18796397261472379","url":null,"abstract":"<p><p>BackgroundRecent reports indicated that 4',5,7-trihydroxyisoflavone (genistein) can improve biochemical disorders and correct behavioral disturbances in cellular and animal models of Huntington's disease (HD), acting thorough stimulation of autophagy-dependent degradation of mutant huntingtin aggregates. Effects in the mouse HD model was tested previously only after appearance of symptoms of HD.ObjectiveThe aim of this work was to assess the efficacy of genistein in preventing the appearance of symptoms in the R6/1 mouse model of HD, using both males and females.MethodsA battery of behavioral tests (Rota-rod, elevated-plus maze, Morris water maze, monitoring of movements in actometer) was used, and selected biochemical and hematological parameters were determined in control (wild-type) and R6/1 (HD) mice (males and females) treated with either orally-administered genistein at 150 mg/kg/day or water (control). The treatment was initiated at 7^th week of life (while the first symptoms appear at 14-16 week in this HD model), and was continued until 30^th week.ResultsAdministration of genistein resulted in extension of life span and prevention of appearance of HD symptoms in R6/1 mice. The immunological and biochemical parameters were comparable between wild-type and R6/1 mice treated with genistein, whereas the untreated HD animals revealed significant differences relative to controls.ConclusionsGenistein appeared to be effective in preventing the appearance of severe symptoms of HD in the mouse R6/1 model, indicating that this compound might be considered as a potential anti-HD drug.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261472379"},"PeriodicalIF":2.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591786","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":"Machine learning applications in Huntington's disease prognosis: A review.","authors":"Lubna M Abu Zohair, Ruben Andriessen, Noor Mahmoud, Moram Khalid, Hind Zantout, Marta Vallejo","doi":"10.1177/18796397261468824","DOIUrl":"https://doi.org/10.1177/18796397261468824","url":null,"abstract":"<p><p>Understanding the trajectory of Huntington's disease (HD) is critical for patient stratification and the development of targeted interventions. Traditionally, studies relied on age-CAG models to estimate disease onset and progression, based on the well-established relationship between CAG repeat length and age at onset. However, additional genetic, environmental, and clinical factors can cause substantial variability. Recent machine learning approaches integrate clinical, imaging, and molecular data for more precise prediction of disease progression. Following PRISMA guidelines, we systematically reviewed studies on HD onset and progression. Using Web of Science, PubMed, and IEEE Xplore, 20 studies published between 2003 and 2024 met the inclusion criteria. We analyzed the machine learning approaches and input features used, assessed methodological quality, and evaluated risk of bias using the PROBAST tool. Overall, machine learning models, particularly support vector machines and ensemble approaches, consistently outperformed traditional age-CAG models. Several studies predicted conversion from premanifest to manifest HD within 5-10 years with high accuracy (88-98%). Beyond predicting onset, machine learning models have also been used to model dis-ease progression using clinical scores assessing motor, cognitive, and functional impairment. Performance was higher in studies incorporating structural and functional MRI biomarkers, and improved further with longitudinal clinical integration, enabling pre-diction of decline years before symptoms onset. Overall, machine learning shows strong potential to improve prognostic modeling in HD, especially through multimodal and longitudinal data. However, common methodological weaknesses and bias highlight the need for larger, externally validated studies using objective biomarkers.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261468824"},"PeriodicalIF":2.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536125","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":"Practical recommendations for the treatment of chorea associated with Huntington's disease: An expert consensus.","authors":"Erin Furr Stimming, Jee Bang, Amy Brown, Bisena Bulica, Samuel Frank, David Houghton, Nikolaus R McFarland, Tiago A Mestre, Stephen Aradi, Victor Sung, Daniel Claassen","doi":"10.1177/18796397261468482","DOIUrl":"10.1177/18796397261468482","url":null,"abstract":"<p><p>Huntington's disease (HD) is a rare, autosomal dominant neurodegenerative disorder caused by a pathogenic CAG expansion in the huntingtin gene, classically characterized by a triad of cognitive, psychiatric, and motor symptoms. Involuntary movements known as chorea are the most notable feature of HD. Despite the negative impact chorea can have on many aspects of day-to-day life, pharmacologic treatment remains underutilized in clinical practice. Barriers include anosognosia, a complex treatment landscape, limited evidence-based guidelines, and variable access to care. In February 2025, 11 North American HD specialists and members of the Huntington Study Group (HSG) Motor Treatment Task Force, who collectively care for ∼1500 people with HD (PwHD) convened to discuss current practices and challenges in the pharmacologic treatment of chorea. Insights were supplemented by responses to a long-form questionnaire distributed via email. Attendees and respondents described practical approaches to assessing chorea, engaging care partners, and setting goal-oriented treatment plans. This review draws on collective experience to highlight practical, real-world strategies for the evaluation and treatment of HD chorea. The two most common medication classes used to suppress chorea are vesicular monoamine transporter 2 (VMAT2) inhibitors and antipsychotics. Individualized titration, regular patient and care partner feedback, and functional, rather than purely motor-based, assessments are key to optimizing therapy. By integrating pharmacologic therapy with multidisciplinary care and holistic, goal-oriented communication about the impact of chorea, clinicians can meaningfully improve safety, independence, and quality of life for individuals and families affected by HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261468482"},"PeriodicalIF":2.7,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436833","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":"Phase-targeted auditory stimulation enhances slow-wave activity during sleep in Huntington's disease: A pilot crossover study.","authors":"Andreas A Braun, Jonas Buff, Nora-Hjördis Moser, Renske Sassenburg, Nils Briel, Angelina Maric, Simon J Schreiner, Hans H Jung","doi":"10.1177/18796397261464670","DOIUrl":"https://doi.org/10.1177/18796397261464670","url":null,"abstract":"<p><p>BackgroundSleep disturbances, including fragmentation and reduced slow-wave sleep (SWS), are common in Huntington's disease (HD). SWS contributes to synaptic homeostasis, metabolic clearance, and memory consolidation. Phase-targeted auditory stimulation (PTAS) enhances slow-wave activity (SWA) in healthy individuals and Parkinson's disease, but its feasibility and physiological effects in HD remain unknown.ObjectiveTo assess the feasibility and physiological effects of PTAS in individuals with HD in a home-based setting.MethodsTen participants with genetically confirmed HD were enrolled in a randomized, double-blind, sham-controlled crossover pilot study conducted at home. After a test night, participants completed one sham and one verum night using a wearable sleep device. Auditory stimuli (pink-noise bursts) were delivered in alternating 6-s ON and OFF windows targeting the up-phase of slow waves during non-rapid eye movement sleep. SWA (0.5-4.5 Hz) and frequency-resolved EEG power were analyzed using linear mixed-effects models.ResultsFive participants completed the protocol and were included in the analysis. Four showed higher SWA during ON compared with OFF windows during verum nights. Frequency-resolved analyses demonstrated increased delta-band power during ON windows relative to sham. No relevant differences in sleep macrostructure were observed between verum and sham nights, although interpretation was limited by the small sample size and participant heterogeneity. Completion was limited by device discomfort, external factors, and technical issues.ConclusionPTAS transiently enhances SWA during stimulation windows in some individuals with HD in an at-home setting. Larger studies are needed to identify predictors of response and determine clinical relevance.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261464670"},"PeriodicalIF":2.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375992","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":"Differential sensitivity of the MMSE and MoCA for staging and longitudinal cognitive change in Huntington's disease.","authors":"Krisha Bagga, Ben Shifflett, Anvit Sidhu, Paul E Gilbert, Jody Corey-Bloom","doi":"10.1177/18796397261461641","DOIUrl":"https://doi.org/10.1177/18796397261461641","url":null,"abstract":"<p><p>ObjectiveTo compare the sensitivity of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) for detecting cognitive change in Huntington's disease (HD) subjects stratified by baseline performance quartiles and the Huntington's Disease Integrated Staging System (HD-ISS).MethodsParticipants (age 25-65; CAG 40-50) from an observational cohort completed MMSE and MoCA at baseline, with follow-up visits at least six months after baseline, and observations truncated at five years.We analyzed the full cohort (n = 246) and an HD-ISS-staged subset (n = 132). Longitudinal change was evaluated using mixed-effects models, adjusted for baseline age, gender, education, CAG, and age × CAG interaction. Baseline discrimination between HD-ISS stages was assessed with ROC curves and AUC comparisons.ResultsAnnual decline was nearly identical for MMSE and MoCA (-0.334 vs. -0.331). Adjusted quartile analyses revealed differential sensitivity: MoCA showed greater decline in lower and higher performance levels (Quartiles 1, 3, and 4), while MMSE was most sensitive at mid-range (Quartile 2). In HD-ISS analyses, MMSE demonstrated more consistent decline across stages, particularly Stages 1 and 3, indicating sensitivity to early and moderate disease phases. Baseline ROC analyses favored MoCA for stage discrimination (Stage 0 vs. all: AUC 0.789 vs. 0.686, p = 0.011).ConclusionThe MMSE and MoCA exhibit complementary strengths. MoCA demonstrates superior sensitivity for baseline staging and early disease detection, while MMSE better captures longitudinal decline. These findings suggest that combined use of both instruments may provide a more complete assessment of cognitive progression in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261461641"},"PeriodicalIF":2.7,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345482","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 cortical development sets the stage in Huntington disease.","authors":"Marine Degennaro, Sandrine Humbert, Mariacristina Capizzi","doi":"10.1177/18796397261426033","DOIUrl":"10.1177/18796397261426033","url":null,"abstract":"<p><p>One of the great mysteries of Huntington disease (HD) is its adult onset. HD is caused by a CAG repeat expansion in the <i>HTT</i> gene, which encodes a protein (HTT) that is crucial for intracellular transport and neuronal growth, so one would expect development to be altered in some way. Human fetal samples, cell and animal model studies have shown that neurodevelopment is indeed altered in HD. Structural and functional abnormalities can be detected during the presymptomatic phase, and mutation carriers may display subtle cognitive deficits, psychiatric disturbances, or motor impairments years before clinical diagnosis. However, despite these early developmental alterations and the lifelong presence of mutant huntingtin (mHTT), HD carriers typically experience a long asymptomatic period. In this review, we provide an overview of the functions of HTT and the dysfunctions caused by mHTT or HTT loss during development, from gastrulation to neurulation, and examine the specific contribution of the cerebral cortex in HD. Drawing on nearly 25 years of research, we integrate studies ranging from in vitro to in vivo studies, highlighting the molecular mechanisms that contribute to HD neuropathology. Understanding these early developmental processes may define a window for therapeutic intervention, a period of plasticity during which the brain may still correct or compensate for developmental errors. This could strengthen the foundations to extend the presymptomatic phase and delay neurodegeneration.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"275-285"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306911","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}