Journal of Huntington's Disease

BACKGROUND: In healthy people, sleep and circadian disruption are linked to cognitive deficits. People with Huntington's disease (HD), who have compromised brain function and sleep and circadian disturbances, may be even more susceptible to these cognitive effects. OBJECTIVE: To conduct a comprehensive review and synthesis of the literature in HD on the associations of cognitive dysfunction with disturbed sleep and circadian rhythms. METHODS: We searched MEDLINE via OVID, CINAHL Plus, EMBASE via OVID, and PubMed in May 2023...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the GENERATION HD2 (tominersen) and on the Asklepios Biopharmaceutical/BrainVectis trial with AB-1001. We also comment on the recent findings from the PROOF-HD trial, and list all currently registered and ongoing clinical trials in Huntington's disease.

Sleep and circadian alterations are common in patients with Huntington's disease (HD). Understanding the pathophysiology of these alterations and their association with disease progression and morbidity can guide HD management. We provide a narrative review of the clinical and basic-science studies centered on sleep and circadian function on HD. Sleep/wake disturbances among HD patients share many similarities with other neurodegenerative diseases. Overall, HD patients and animal models of the disease present with sleep changes early in the clinical course of the disease, including difficulties with sleep initiation and maintenance leading to decreased sleep efficiency, and progressive deterioration of normal sleep architecture...

Sleep disorders are common in Huntington's disease (HD) but are complex; their bi-directional associations with psychiatric, cognitive, and motor dysfunction makes them especially important to both consider and to treat. The author provides a perspective in brief regarding sleep disturbances in HD, based on her experience caring for, and learning from, patients with HD for more than twenty years.

BACKGROUND: Families in which a parent has Huntington's disease (HD) are faced with significant stressors that can contribute to difficulties in communicating together about illness-related concerns. Family members who use more disengagement coping strategies, including denial and avoidance, to deal with illness-related stressors may have the greatest challenges to effective communication. OBJECTIVE: The current study examined the associations of intrapersonal and interpersonal disengagement coping responses with observed and reported emotions of adolescents and young adults (AYA) at genetic risk for HD...

Sleep and circadian disruption affects most individuals with Huntington's disease (HD) at some stage in their lives. Sleep and circadian dysregulation are also present in many mouse and the sheep models of HD. Here I review evidence for sleep and/or circadian dysfunction in HD transgenic animal models and discuss two key questions: 1) How relevant such findings are to people with HD, and 2) Whether or not therapeutic interventions that ameliorate deficits in animal models of HD might translate to meaningful therapies for people with HD...

Sleep occupies a peculiar place in our lives and in science, being both eminently familiar and profoundly enigmatic. Historically, philosophers, scientists and artists questioned the meaning and purpose of sleep. If Shakespeare's verses from MacBeth depicting "Sleep that soothes away all our worries" and "relieves the weary laborer and heals hurt minds" perfectly epitomize the alleviating benefits of sleep, it is only during the last two decades that the growing understanding of the sophisticated sleep regulatory mechanisms allows us to glimpse putative biological functions of sleep...

Sleep dysfunction is highly prevalent in Huntington's disease (HD). Increasing evidence suggests that such dysfunction not only impairs quality of life and exacerbates symptoms but may even accelerate the underlying disease process. Despite this, current HD treatment approaches neither consider the impact of commonly used medications on sleep, nor directly tackle sleep dysfunction. In this review, we discuss approaches to these two areas, evaluating not only literature from clinical studies in HD, but also that from parallel neurodegenerative conditions and preclinical models of HD...

BACKGROUND: Prior studies have relied on conventional observer-based severity ratings such as the Unified Huntington's Disease Rating Scale (UHDRS) to identify early motor markers of decline in Huntington's disease (HD). OBJECTIVE: The present study examined the predictive utility of graphomotor measures handwriting and drawing movements. METHODS: Seventeen gene-positive premanifest HD subjects underwent comprehensive clinical, cognitive, motor, and graphomotor assessments at baseline and at follow-up intervals ranging from 9-36 months...

No abstract text is available yet for this article.

Our physiology and behavior follow precise daily programs that adapt us to the alternating opportunities and challenges of day and night. Under experimental isolation, these rhythms persist with a period of approximately one day (circadian), demonstrating their control by an internal autonomous clock. Circadian time is created at the cellular level by a transcriptional/translational feedback loop (TTFL) in which the protein products of the Period and Cryptochrome genes inhibit their own transcription. Because the accumulation of protein is slow and delayed, the system oscillates spontaneously with a period of ∼24 hours...

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The disease, characterized by motor, cognitive, and psychiatric impairments, is caused by the expansion of a CAG repeat in the huntingtin gene. Despite the discovery of the mutation in 1993, no disease-modifying treatments are yet available. Understanding the molecular and cellular mechanisms involved in HD is therefore crucial for the development of novel treatments. Emerging research has found that HD might be classified as a secondary tauopathy, with the presence of tau insoluble aggregates in late HD...

Recent years have been turbulent ones for the Huntington's disease (HD) community. Three clinical trials for HD, including the first Phase 3 trial of a potentially disease modifying genetic therapy for HD, were all brought to a halt in March of 2021. 2022 brought more study roadblocks and an additional trial termination. As HD science progresses and larger scale trials become more frequent in the community, HD families are faced with the difficult reality that clinical research rarely results in a new drug hitting the market...

BACKGROUND: Gastrointestinal symptoms are clinical features of Huntington's disease (HD), which adversely affect people's quality of life. We recently reported the first evidence of gut dysbiosis in HD gene expansion carriers (HDGECs). Here, we report on a randomized controlled clinical trial of a 6-week probiotic intervention in HDGECs. OBJECTIVE: The primary objective was to determine whether probiotics improved gut microbiome composition in terms of richness, evenness, structure, and diversity of functional pathways and enzymes...

Advance care planning (ACP) is a useful tool that benefits adult patients, care providers, and surrogate decision makers, through providing opportunities for patients to consider, express, and formalize their beliefs, preferences, and wishes pertaining to decisions regarding future medical care at a time when they retain decision-making capacity. Early and timely consideration of ACP discussions is paramount in Huntington's disease (HD) given the potential challenges in ascertaining decision-making capacity in the advanced stages of the disease...

There is increasing evidence for the presence of pathological forms of tau in tissues of both Huntington's disease (HD) patients and animal models of this condition. While cumulative studies of the past decade have led to the proposition that this disorder could also be considered a tauopathy, the implications of tau in cellular toxicity and consequent behavioral impairments are largely unknown. In fact, recent animal work has challenged the contributory role of tau in HD pathogenesis/pathophysiology. This review presents the supporting and opposing arguments for the involvement of tau in HD, highlighting the discrepancies that have emerged...

BACKGROUND: Metabolic abnormalities have long been predicted in Huntington's disease (HD) but remain poorly characterized. Chronobiological dysregulation has been described in HD and may include abnormalities in circadian-driven metabolism. OBJECTIVE: Here we investigated metabolite profiles in the transgenic sheep model of HD (OVT73) at presymptomatic ages. Our goal was to understand changes to the metabolome as well as potential metabolite rhythm changes associated with HD...

BACKGROUND: Huntington's disease (HD) is a genetic neurodegenerative disease caused by trinucleotide repeat CAG expansions in the human HTT gene. Early onset juvenile HD (JHD) in children is the most severe form of the disease caused by high CAG repeat numbers of the HTT gene. OBJECTIVE: To gain understanding of human HD mechanisms hypothesized to involve dysregulated proteomes of brain regions that regulate motor and cognitive functions, this study analyzed the proteomes of human JHD cortex and putamen brain regions compared to age-matched controls...