Journal of Huntington's disease最新文献

{"title":"Huntington's Disease Regulatory Science Consortium: Accelerating Medical Product Development.","authors":"Emily C. Turner, Emily C. Gantman, C. Sampaio, Sudhir Sivakumaran","doi":"10.3233/jhd-220533","DOIUrl":"https://doi.org/10.3233/jhd-220533","url":null,"abstract":"Huntington's disease (HD) is a devastating neurodegenerative disorder that urgently needs disease-modifying therapeutics. To this end, collaboration to standardize clinical research practices in the field and drive progress in addressing drug development challenges is paramount. At a meeting in 2017 organized by CHDI Foundation and the Critical Path Institute, stakeholders across the pharmaceutical industry, academia, regulatory agencies, and patient advocacy groups discussed the need for and potential impact of a consortium dedicated to HD regulatory science. Consequently, the Huntington's Disease Regulatory Science Consortium (HD-RSC) was formed, a precompetitive consortium that is dedicated to building a regulatory strategy to expedite the approval of HD therapeutics.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43823001","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":"Standardizing the CAP Score in Huntington's Disease by Predicting Age-at-Onset.","authors":"John H. Warner, J. Long, J. Mills, D. Langbehn, Jennifer J. Ware, A. Mohan, C. Sampaio","doi":"10.3233/jhd-210475","DOIUrl":"https://doi.org/10.3233/jhd-210475","url":null,"abstract":"BACKGROUND\u0000Huntington's disease (HD) is an autosomal dominant, neurological disease caused by an expanded CAG repeat near the N-terminus of the huntingtin (HTT) gene. A leading theory concerning the etiology of HD is that both onset and progression are driven by cumulative exposure to the effects of mutant (or CAG expanded) huntingtin (mHTT). The CAG-Age-Product (CAP) score (i.e., the product of excess CAG length and age) is a commonly used measure of this cumulative exposure. CAP score has been widely used as a predictor of a variety of disease state variables in HD. The utility of the CAP score has been somewhat diminished, however, by a lack of agreement on its precise definition. The most commonly used forms of the CAP score are highly correlated so that, for purposes of prediction, it makes little difference which is used. However, reported values of CAP scores, based on commonly used definitions, differ substantially in magnitude when applied to the same data. This complicates the process of inter-study comparison.\u0000\u0000\u0000OBJECTIVE\u0000In this paper, we propose a standardized definition for the CAP score which will resolve this difficulty. Our standardization is chosen so that CAP = 100 at the expected age of diagnosis.\u0000\u0000\u0000METHODS\u0000Statistical methods include novel survival analysis methodology applied to the 13 disease landmarks taken from the Enroll-HD database (PDS 5) and comparisons with the existing, gold standard, onset model.\u0000\u0000\u0000RESULTS\u0000Useful by-products of our work include up-to-date, age-at-onset (AO) results and a refined AO model suitable for use in other contexts, a discussion of several useful properties of the CAP score that have not previously been noted in the literature and the introduction of the concept of a toxicity onset model.\u0000\u0000\u0000CONCLUSION\u0000We suggest that taking L = 30 and K = 6.49 provides a useful standardization of the CAP score, suitable for use in the routine modeling of clinical data in HD.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44764005","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 Hold me Tight Program for Couples Facing Huntington's Disease.","authors":"Tara M Petzke, M. Rodríguez-Girondo, L. B. van der Meer","doi":"10.3233/jhd-210516","DOIUrl":"https://doi.org/10.3233/jhd-210516","url":null,"abstract":"BACKGROUND A positive predictive genetic test for Huntington's disease (HD) can be a life-changing event for both carriers and their partners, leading to lower wellbeing and increasing the risk for separation and divorce. The 'Hold me Tight' program (HmT), based on emotionally focused couples' therapy, aims at strengthening the couple bond by targeting attachment needs. OBJECTIVE This study investigates whether the HmT program helps couples strengthen their relationship, as an investment in a future where the disease will affect life in many ways. METHODS In a multiple baseline design using three baselines of varying length, 15 couples of presymptomatic HD-carriers and their partners were included. In three consecutive groups, couples underwent the intervention (an adapted version of the 8-session HmT program) in four weekly sessions and completed self-report questionnaires throughout the study period of 19 weeks (17 measurements). Attachment style was assessed at baseline, resilience at baseline and at the end of the follow-up, while relationship satisfaction and wellbeing were measured weekly. A multi-level model was applied to the data. RESULTS Over the course of the study, wellbeing and relationship satisfaction significantly improved; resilience, however, did not. Furthermore, all three outcome measures were moderated by attachment style, with more securely attached individuals showing better outcomes. CONCLUSION HmT improved wellbeing and relationship satisfaction of couples facing HD. Due to these improvements and high patient acceptability rates, this program could become a standardized procedure in HD care. The program could be adapted for other populations, e.g., couples facing other genetic neurological disorders.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41531112","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":"Disease Burden of Huntington’s Disease (HD) on People Living with HD and Care Partners in Canada","authors":"E. Shaw, Michelle Mayer, P. Ekwaru, S. McMullen, E. Graves, Jennifer W. Wu, Nathalie Budd, B. Maturi, T. Cowling, T. Mestre","doi":"10.3233/jhd-210505","DOIUrl":"https://doi.org/10.3233/jhd-210505","url":null,"abstract":"Background: Huntington’s disease (HD) has been shown to reduce health-related quality of life (HRQoL) and affect healthcare resource utilization (HRU) among patients and care partners internationally but has not been studied specifically in the Canadian context. Objective: To characterize the burden of HD on individuals with HD and care partners of individuals with HD in Canada. Methods: An online survey was distributed (September 14–November 23, 2020) through patient organizations to collect data on demographic and clinical characteristics, as well as: HRQoL, measured using the 36-Item Short-Form Health Survey (SF-36v1); HRU, measured using the Client Service Receipt Inventory (CSRI); and care partner burden, measured using the Caregiver Strain Index (CSI) and Huntington’s Disease Quality of Life Battery for Carers (HDQoL-C). Descriptive statistics were used to report data and compare subgroups. Results: A total of 62 adult individuals with HD (or their proxies) and 48 care partners met defined eligibility criteria. The mean [standard deviation] age was 51.2 [13.8] and 58.1 [13.9] years for individuals with HD and care partner respondents, respectively. For individuals with HD, the greatest HRQoL burden (i.e., lowest score) was for the SF-36v1 Role –Physical scale (46.8 [42.9]). HRU was higher for some services (e.g., general practitioner visits) for respondents who had experienced motor onset transition. Among care partners, 55.3% experienced high strain, as indicated by the CSI. The HDQoL-C showed the greatest HRQoL burden in feelings about life (45.1 [17.9]). Conclusion: This study quantified the substantial burden on individuals with HD and care partners in Canada, addressing a critical knowledge gap that can affect the availability of and access to healthcare services.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46949539","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 message from the Editors-in-Chief on the 10th Anniversary of the Journal of Huntington's Disease.","authors":"B. Leavitt, L. Thompson","doi":"10.3233/jhd-229001","DOIUrl":"https://doi.org/10.3233/jhd-229001","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45059071","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":"Geographic Barriers Drive Disparities in Specialty Center Access for Older Adults with Huntington's Disease.","authors":"Thanh Phuong Pham Nguyen, Licia Bravo, P. Gonzalez-Alegre, A. Willis","doi":"10.3233/jhd-210489","DOIUrl":"https://doi.org/10.3233/jhd-210489","url":null,"abstract":"BACKGROUND\u0000Huntington's Disease Society of America Centers of Excellence (HDSA COEs) are primary hubs for Huntington's disease (HD) research opportunities and accessing new treatments. Data on the extent to which HDSA COEs are accessible to individuals with HD, particularly those older or disabled, are lacking.\u0000\u0000\u0000OBJECTIVE\u0000To describe persons with HD in the U.S. Medicare program and characterize this population by proximity to an HDSA COE.\u0000\u0000\u0000METHODS\u0000We conducted a cross-sectional study of Medicare beneficiaries ages ≥65 with HD in 2017. We analyzed data on benefit entitlement, demographics, and comorbidities. QGis software and Google Maps Interface were employed to estimate the distance from each patient to the nearest HDSA COE, and the proportion of individuals residing within 100 miles of these COEs at the state level.\u0000\u0000\u0000RESULTS\u0000Among 9,056 Medicare beneficiaries with HD, 54.5% were female, 83.0% were white; 48.5% were ≥65 years, but 64.9% originally qualified for Medicare due to disability. Common comorbidities were dementia (32.4%) and depression (35.9%), and these were more common in HD vs. non-HD patients. Overall, 5,144 (57.1%) lived within 100 miles of a COE. Race/ethnicity, sex, age, and poverty markers were not associated with below-average proximity to HDSA COEs. The proportion of patients living within 100 miles of a center varied from < 10% (16 states) to > 90% (7 states). Most underserved states were in the Mountain and West Central divisions.\u0000\u0000\u0000CONCLUSION\u0000Older Medicare beneficiaries with HD are frequently disabled and have a distinct comorbidity profile. Geographical, rather than sociodemographic factors, define the HD population with limited access to HDSA COEs.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41302081","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":"Recent Microscopy Advances and the Applications to Huntington's Disease Research.","authors":"Mouhanad Babi,&nbsp;Kaitlyn Neuman,&nbsp;Christina Y Peng,&nbsp;Tamara Maiuri,&nbsp;Celeste E Suart,&nbsp;Ray Truant","doi":"10.3233/JHD-220536","DOIUrl":"https://doi.org/10.3233/JHD-220536","url":null,"abstract":"<p><p>Huntingtin is a 3144 amino acid protein defined as a scaffold protein with many intracellular locations that suggest functions in these compartments. Expansion of the CAG DNA tract in the huntingtin first exon is the cause of Huntington's disease. An important tool in understanding the biological functions of huntingtin is molecular imaging at the single-cell level by microscopy and nanoscopy. The evolution of these technologies has accelerated since the Nobel Prize in Chemistry was awarded in 2014 for super-resolution nanoscopy. We are in a new era of light imaging at the single-cell level, not just for protein location, but also for protein conformation and biochemical function. Large-scale microscopy-based screening is also being accelerated by a coincident development of machine-based learning that offers a framework for truly unbiased data acquisition and analysis at very large scales. This review will summarize the newest technologies in light, electron, and atomic force microscopy in the context of unique challenges with huntingtin cell biology and biochemistry.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/37/jhd-11-jhd220536.PMC9484089.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40515396","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":"Clinical and Genetic Aspects of Huntington's Disease in the Malian Population.","authors":"Abdoulaye Bocoum,&nbsp;Toumany Coulibaly,&nbsp;Madani Ouologuem,&nbsp;Lassana Cissé,&nbsp;Seybou H Diallo,&nbsp;Boubacar B Maiga,&nbsp;Kékouta Dembélé,&nbsp;Salimata Diallo,&nbsp;Souleymane Dit Papa Coulibaly,&nbsp;Fousseyni Kané,&nbsp;Thomas Coulibaly,&nbsp;Dramane Coulibaly,&nbsp;Abdoulaye Taméga,&nbsp;Abdoulaye Yalcouyé,&nbsp;Salimata Diarra,&nbsp;Mohamed E Dembélé,&nbsp;Alassane B Maiga,&nbsp;Cheick A K Cissé,&nbsp;Oumou Traoré,&nbsp;Kenneth H Fischbeck,&nbsp;Cheick O Guinto,&nbsp;Youssoufa Maiga,&nbsp;Guida Landouré","doi":"10.3233/JHD-220529","DOIUrl":"https://doi.org/10.3233/JHD-220529","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by mutation in the HTT gene and characterized by involuntary movements as well as cognitive and behavioral impairment. Since its first description 150 years ago, studies have been reported worldwide. However, genetically confirmed cases have been scarce in Africa.</p><p><strong>Objective: </strong>To describe the clinical and genetic aspects of HD in the Malian population.</p><p><strong>Methods: </strong>Patients with HD phenotype and their relatives were enrolled after obtaining consent. Symptoms were assessed using the Total Motor Scale (TMS) of the United Huntington's Disease Rating Scale (UHDRS) and the Mini-Mental State Examination (MMSE). Brain imaging and blood tests were performed to exclude other causes. DNA was extracted for HTT sequencing.</p><p><strong>Results: </strong>Eighteen patients (13 families) with a HD phenotype were evaluated. A familial history of the disease was found in 84.6% with 55.5% of maternal transmission. The average length of the HTT CAG repeat was 43.6±11.5 (39-56) CAGs. The mean age at onset was 43.1±9.7years. Choreic movements were the predominant symptoms (100% of the cases) with an average TMS of 49.4±30.8, followed by cognitive impairment (average MMSE score: 23.0±12.0) and psychiatric symptoms with 22.2% and 44.4%, respectively.</p><p><strong>Conclusion: </strong>This is one of the largest HD cohorts reported in Africa. Increasing access to genetic testing could uncover many other HD cases and disease-modifying genetic variants. Future haplotype and psychosocial studies may inform the origin of the Malian mutation and the impact of the disease on patients and their relatives.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40309509","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":"Huntingtin Overexpression Does Not Alter Overall Survival in Murine Cancer Models.","authors":"Laura Lynn Chan,&nbsp;Austin Hill,&nbsp;Ge Lu,&nbsp;Jeremy Van Raamsdonk,&nbsp;Randy Gascoyne,&nbsp;Michael R Hayden,&nbsp;Blair R Leavitt","doi":"10.3233/JHD-220554","DOIUrl":"https://doi.org/10.3233/JHD-220554","url":null,"abstract":"<p><p>A reduced incidence of various forms of cancer has been reported in Huntington's disease patients and may be due to pro-apoptotic effects of mutant huntingtin. We tested this hypothesis by assessing the effects of huntingtin protein overexpression on survival in two murine cancer models. We generated YAC HD mice containing human huntingtin transgenes with various CAG tract lengths (YAC18, YAC72, YAC128) on either an Msh2 or p53 null background which have increased cancer incidence. In both mouse models of cancer, the overexpression of either mutant or wild-type huntingtin had no significant effect on overall survival. These results do not support the hypothesis that mutant huntingtin expression is protective against cancer.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10452272","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":"Lesley Jones: In Memoriam.","authors":"Anne Rosser,&nbsp;Sarah Tabrizi","doi":"10.3233/JHD-229007","DOIUrl":"https://doi.org/10.3233/JHD-229007","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10383537","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}