Journal of Huntington's Disease - Volume 11, issue 4

Authors: Rosser, Anne | Tabrizi, Sarah

Article Type: Obituary

DOI: 10.3233/JHD-229007

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 349-350, 2022

Authors: Estevez-Fraga, Carlos | Tabrizi, Sarah J. | Wild, Edward J.

Article Type: Other

Abstract:  In this edition of the Huntington’s Disease Clinical Trials Corner, we expand on the PIVOT HD (PTC518), and SIGNAL (pepinemab) trials, and list all currently registered and ongoing clinical trials in Huntington’s disease. We also introduce a ‘breaking news’ section highlighting recent updates about the SELECT HD, uniQure AMT-130, and VIBRANT HD clinical trials.

Keywords: Huntington’s disease , clinical trials

DOI: 10.3233/JHD-229006

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 351-367, 2022

Authors: Serbin, Kenneth P.

Article Type: Other

Abstract: This article describes how the author, a Huntington’s disease (HD) gene expansion carrier and long-time advocate, has helped give voice to the HD community through his blog, At Risk for Huntington ’s Disease . Since 2005, the 321 articles have helped document the new and harrowing experience of living in the gray zone between a genetic test result and disease onset. At Risk for HD has explored major challenges for the HD community, has become a key reference for HD families, and has chronicled the quest to defeat the disease. This article analyzes the blog’s thematic impact.

Keywords: Huntington’s disease, Gene Veritas, blog, genetic testing, science reporting, therapies, stigma, support network, patient advocacy

DOI: 10.3233/JHD-220551

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 369-371, 2022

Authors: Hendel, Rebecca K. | Hellem, Marie N.N. | Hjermind, Lena E. | Nielsen, Jørgen E. | Vogel, Asmus

Article Type: Research Article

Abstract: Background: Autonomy describes a psychological state of self-regulation of motivation and action, which is a central characteristic of healthy functioning. In neurodegenerative diseases measures of self-perception have been found to be affected by the disease. However, it has never been investigated whether measures of self-perception, like autonomy, is affected in Huntington’s disease. Objective: We investigated whether autonomy is affected in Huntington’s disease and if the degree of autonomy is associated with motor function, neuropsychiatric symptoms, cognitive impairments, and apathy. Methods: We included 44 premanifest and motor-manifest Huntington’s disease gene expansion carriers and 19 controls. Autonomy was …examined using two self-report questionnaires, the Autonomy-Connectedness Scale-30 and the Index of Autonomous Functioning. All participants were examined according to motor function, cognitive impairments, and neuropsychiatric symptoms, including apathy. Results: Statistically significant differences were found between motor-manifest Huntington’s disease gene expansion carriers and premanifest Huntington’s disease gene expansion carriers or controls on two measures of autonomy. Between 25–38% of motor-manifest Huntington’s disease gene expansion carriers scored significantly below the normal level on subscales of autonomy as compared to controls. One autonomy subscale was associated with apathy (r  = –0.65), but not with other symptoms of Huntington’s disease. Conclusion: This study provides evidence for impaired autonomy in individuals with Huntington’s disease and an association between autonomy and apathy. The results underline the importance of maintaining patient autonomy and involvement in care throughout the disease. Show more

Keywords: Apathy, autonomy, Huntington’s disease, neuropsychiatric symptoms, self-perception

DOI: 10.3233/JHD-220540

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 373-381, 2022

Authors: Chan, Laura Lynn | Hill, Austin | Lu, Ge | Van Raamsdonk, Jeremy | Gascoyne, Randy | Hayden, Michael R. | Leavitt, Blair R.

Article Type: Short Communication

Abstract: 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. Show more

Keywords: Huntington’s disease, cancer, tumorigenesis, mouse models, huntingtin, apoptosis

DOI: 10.3233/JHD-220554

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 383-389, 2022

Authors: Taghian, Toloo | Gallagher, Jillian | Batcho, Erin | Pullan, Caitlin | Kuchel, Tim | Denney, Thomas | Perumal, Raj | Moore, Shamika | Muirhead, Robb | Herde, Paul | Johns, Daniel | Christou, Chris | Taylor, Amanda | Passler, Thomas | Pulaparthi, Sanjana | Hall, Erin | Chandra, Sundeep | O’Neill, Charles A. | Gray-Edwards, Heather

Article Type: Research Article

Abstract: Background: Huntington’s disease (HD) is a fatal neurodegenerative autosomal dominant disorder with prevalence of 1 : 20000 that has no effective treatment to date. Translatability of candidate therapeutics could be enhanced by additional testing in large animal models because of similarities in brain anatomy, size, and immunophysiology. These features enable realistic pre-clinical studies of biodistribution, efficacy, and toxicity. Objective and Methods: Here we non-invasively characterized alterations in brain white matter microstructure, neurochemistry, neurological status, and mutant Huntingtin protein (mHTT) levels in cerebrospinal fluid (CSF) of aged OVT73 HD sheep. Results: Similar to HD patients, CSF mHTT differentiates HD …from normal sheep. Our results are indicative of a decline in neurological status, and alterations in brain white matter diffusion and spectroscopy metric that are more severe in aged female HD sheep. Longitudinal analysis of aged female HD sheep suggests that the decline is detectable over the course of a year. In line with reports of HD human studies, white matter alterations in corpus callosum correlates with a decline in gait of HD sheep. Moreover, alterations in the occipital cortex white matter correlates with a decline in clinical rating score. In addition, the marker of energy metabolism in striatum of aged HD sheep, shows a correlation with decline of clinical rating score and eye coordination. Conclusion: This data suggests that OVT73 HD sheep can serve as a pre-manifest large animal model of HD providing a platform for pre-clinical testing of HD therapeutics and non-invasive tracking of the efficacy of the therapy. Show more

Keywords: Huntington’s disease, transgenic OVT73 sheep model of Huntington’s disease, diffusion tensor imaging, magnetic resonance spectroscopy, large animal model, clinical translation

DOI: 10.3233/JHD-220526

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 391-406, 2022

Authors: Li, Xiao-Yan | Bao, Yu-Feng | Xie, Juan-Juan | Qian, Shu-Xia | Gao, Bin | Xu, Miao | Dong, Yi | Burgunder, Jean-Marc | Wu, Zhi-Ying

Article Type: Research Article

Abstract: Background: The Unified Huntington’s Disease Rating Scale (UHDRS) is a universal scale assessing disease severity of Huntington’s disease (HD). However, the English version cannot be widely used in China, and the reliability and validity of the Chinese UHDRS have not yet been confirmed. Objective: To test the reliability and validity of Chinse UHDRS in patients with HD. Methods: Between August 2013 and August 2021, 159 HD patients, 40 premanifest HD, and 64 healthy controls were consecutively recruited from two medical centers in China and assessed by Chinese UHDRS. Internal consistency and interrater reliability of the scale …were examined. Intercorrelation was performed to analyze the convergent and divergent validity of the scale. A receiver operating characteristic analysis was conducted to explore the optimal cutoff point of each cognitive test. Results: High internal consistency was found in Chinese UHDRS, and its Cronbach’s alpha values of the motor, cognitive, behavioral and functional subscales were 0.954, 0.826, 0.804, and 0.954, respectively. The interrater reliability of the total motor score was 0.960. The convergent and divergent validity revealed that motor, cognitive and functional subscales strongly related to each other except for Problem Behavior Assessment. Furthermore, we not only provided the normal level of each cognitive test in controls, but also gave the optimal cutoff points of cognitive tests between controls and HD patients. Conclusion: We demonstrate for the first time that the translated version of UHDRS is reliable for assessing HD patients in China. This can promote the universal use of UHDRS in clinical practice. Show more

Keywords: Huntington’s disease, UHDRS, Chinese, reliability assessment

DOI: 10.3233/JHD-220542

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 407-413, 2022

Authors: Mohanty, Diksha | Schmitt, Philipp | Dixon, Laura | Holiday, Victoria | Hedera, Peter

Article Type: Research Article

Abstract: Background: The coronavirus pandemic saw technology evolve as outpatient clinics faced restriction of in-person visits. Reliance on telemedicine using two-way audio-video communication significantly increased. Telemedicine was observed to be convenient, cost-effective, reduced no-show rates, and fostered sustained engagement. Enhanced flexibility from short notice scheduling benefitted patients and their caregivers. Greater time value was perceived by patients, and reduced reliance on caregivers. Disadvantages included barriers of access to internet connectivity or equipment. Objective: We aimed to retrospectively survey patients with Huntington’s disease (HD) seen via telehealth in our HDSA Center for Excellence Multidisciplinary clinic. We evaluated usability, learnability, interface …quality, reliability, and future use. Methods: This qualitative survey used the 21-item Telehealth Usability Questionnaire. Close-ended responses ranged from strongly disagree to strongly agree scored on Likert scale (1 through 7). Averages were calculated to examine attitudes towards telemedicine. Spearman correlation test was performed to detect attitude biases between patients and caregivers. Results: Respondents were more likely than not to strongly agree with survey statements. Average attitude score of 5.92 (range 2.95-7.00) suggested favorability and improved convenience when telehealth was used in complement to in-person visits, without detriment to patient-provider communication. Spearman correlation coefficient between patient and family/caregiver groups was 0.023, which is below the cutoff of 0.344 for a  = 0.05 at N  = 24. This suggests there was no bias between patient and caregiver attitudes. Conclusion: This study demonstrated telehealth is favored by caregivers and patients with HD. This population with specific physical, cognitive and psychiatric needs can benefit from adaptive systems that enhance compliance. Show more

Keywords: Telehealth, COVID-19, healthcare accessibility, HDSA, HD clinic

DOI: 10.3233/JHD-220547

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 415-419, 2022

Authors: Carroll, Kelly | Hudek, Natasha | Bénard, Angèle | Presseau, Justin | Richards, Dawn P. | Susan, Marlin | Fergusson, Dean A. | Graham, Ian D. | Mestre, Tiago A. | Brehaut, Jamie C.

Article Type: Research Article

Abstract: Background: Under-recruitment regularly impedes clinical trials, leading to wasted resources and opportunity costs. Methods for designing trial participation strategies rarely consider behavior change theory. Objective: Informed by the Theoretical Domains Framework, we identified factors important to participating in Huntington’s disease research and provide examples of how such a theory-informed approach can make specific suggestions about how to design targeted recruitment strategies. Methods: We identified a range of trial participation barriers and enablers based on interviews of key informants and implemented an online survey of members of the Huntington’s disease community, asking them to rate the extent …to which different factors would affect likelihood to participate in a generic Huntington’s disease trial. Results: From 4,195 members, we received 323 responses and 243 completed surveys (323/4,195 or 8% participation, 243/323 or 75% completion). Respondents endorsed 9 barriers and 23 enablers relevant to trial participation. Most frequently endorsed barriers were travel to the study site (69%), worry about unknown side effects (65%), trial documents being difficult to understand (64%), and participation affecting other activities (49%). Enablers included optimism about likelihood of trial participation leading to a cure (98%), helping others (98%), contributing to science (97%), and having helpful people available to help with the participation decision (89%). Conclusion: Our theory-informed survey to identify barriers to and enablers of Huntington’s disease trial participation identified 32 factors, from 13 theoretical domains relevant to trial participation, and suggests effective approaches for improving trial participation and patient experience. Show more

Keywords: Barriers and enablers to participation, Huntington’s disease, recruitment, survey, theoretical domains framework, theory, trial participation

DOI: 10.3233/JHD-220541

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 421-434, 2022

Authors: Fritz, Nora E. | Kegelmeyer, Deb A. | Rao, Ashwini K. | Quinn, Lori | Kloos, Anne D.

Article Type: Review Article

Abstract: Background: In 2020, our group published physical therapy clinical practice guidelines (CPG) for people with Huntington’s disease (HD). The guideline recommendations were categorized according to six primary movement impairment classifications. Objective: To facilitate implementation of this CPG, we have developed guideline-based algorithms for physical therapy assessments and interventions and recommendations for therapists to overcome barriers to CPG implementation for people with HD. Methods: We conducted a literature review of papers that evaluated physical therapy interventions in individuals with HD (n  = 26) to identify assessments for each of the primary movement impairment classifications, and then searched for …papers (n  = 28) that reported their clinometric/psychometric properties in HD. Assessments were evaluated using modified Movement Disorder Society Committee on Rating Scales criteria and other relevant criteria. Results: We identified a “core set” of physical therapy assessments for persons with HD, including the Six Minute Walk Test, Timed Up and Go Test, Berg Balance Scale, and the Medical Outcomes Study Short Form 36 (SF-36). We then developed guideline-based decision trees to assist in decision making and implementation of the CPG into practice for persons with HD across the continuum of care. Finally, we developed strategies for overcoming barriers to implementation, such as seeking specialized training in HD, engaging caretakers or family members to help the person with HD to exercise, and establishing clinical pathways that support early physical therapy referrals. Conclusion: Knowledge translation documents such as this are essential to promoting implementation of the physical therapy CPGs into clinical practice. Show more

Keywords: Assessment, plan of care, exercise, rehabilitation, algorithms, guidelines

DOI: 10.3233/JHD-220549

Citation: Journal of Huntington's Disease, vol. 11, no. 4, pp. 435-453, 2022