Pridopidine in early-stage manifest Huntington's disease: a phase 3 trial.

Huntington's disease (HD) is a rare, neurodegenerative disorder for which only symptomatic treatments are available. The PROOF-HD study was a randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of pridopidine, a selective Sigma-1 receptor agonist, in HD. The primary and key secondary endpoints, change in total functional capacity (TFC) and composite Unified Huntington's Disease Rating Scale (cUHDRS) score at week 65, were not met in the overall population.

Childhood trauma and psychological distress during adulthood in children from Huntington's disease families: An exploratory retrospective analysis.

BackgroundChildren of people with Huntington's disease (HD) often face a wide range of early psychological challenges which may lead to further psychological difficulties later in life.ObjectiveThis exploratory retrospective study aimed to investigate the relationship between childhood traumatic experiences and psychological difficulties during adulthood in individuals raised in HD families compared to matched controls.MethodsThirty-eight adult children of people with HD and 20 matched controls completed a demographic questionnaire, the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and the Symptom Checklist-90-Revised (SCL-90-R).

"I Wouldn't Even Know What to Ask for": Patients' and Caregivers' Experiences of Psychological Support for Huntington's Disease in Italy.

People with Huntington's disease (HD) often experience psychological difficulties linked with disease progression and the adjustment to living with a chronic condition, which are also frequently shared by their informal caregivers (e.g., partners).

Nuclear proteasomes buffer cytoplasmic proteins during autophagy compromise.

Autophagy is a conserved pathway where cytoplasmic contents are engulfed by autophagosomes, which then fuse with lysosomes enabling their degradation. Mutations in core autophagy genes cause neurological conditions, and autophagy defects are seen in neurodegenerative diseases such as Parkinson's disease and Huntington's disease. Thus, we have sought to understand the cellular pathway perturbations that autophagy-perturbed cells are vulnerable to by seeking negative genetic interactions such as synthetic lethality in autophagy-null human cells using available data from yeast screens.

Development of the Huntington Support App (HD-eHelp study): a human-centered and co-design approach.

Introduction: eHealth seems promising in addressing challenges in the provision of care for Huntington's disease (HD) across Europe. By harnessing information and communication technologies, eHealth can partially relocate care from specialized centers to the patients' home, thereby increasing the availability and accessibility of specialty care services beyond regional borders. Previous research on eHealth (development) in HD is however limited, especially when it comes to including eHealth services specifically designed together with HD gene expansion carriers (HDGECs) and their partners to fit their needs and expectations.

Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease.

Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG expansion on the huntingtin () gene and is characterized by progressive motor, cognitive, and neuropsychiatric decline. Recently, new genetic factors besides CAG repeats have been implicated in the disease pathogenesis. Most genetic modifiers are involved in DNA repair pathways and, as the cause of the loss of CAA interruption in the gene, they exert their main influence through somatic expansion.

Prodromal Cognitive Changes as a Prognostic Indicator of Forthcoming Huntington's Disease Severity: A Retrospective Longitudinal Study.

Background: Cognitive changes in Huntington's disease (HD) precede motor manifestations. ENROLL-HD platform includes four cognitive measures of information processing speed (IPS). Our group is eager to seek clinical markers in the life stage that is as close as possible to the age of onset (ie, the so called prodromal HD phase) because this is the best time for therapeutic interventions.

GLUT-1 changes in paediatric Huntington disease brain cortex and fibroblasts: an observational case-control study.

Background: Paediatric Huntington disease with highly expanded mutations (HE-PHD; >80 CAG repeats) presents atypically, compared to adult-onset Huntington disease (AOHD), with neurodevelopmental delay, epilepsy, abnormal brain glucose metabolism, early striatal damage, and reduced lifespan. Since genetic GLUT-1 deficiency syndrome shows a symptom spectrum similar to HE-PHD, we investigated the potential role of the two main glucose transporters, GLUT-1 and GLUT-3, in HE-PHD.

Methods: We compared GLUT-1 and GLUT-3 protein expression in HE-PHD, juvenile-onset (JOHD), and AOHD brains (n = 2; n = 3; n = 6) and periphery (n = 3; n = 2; n = 2) versus healthy adult controls (n = 6; n = 6).

Validity, diagnostics and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in Huntington's disease.

Background: This study is aimed at assessing the clinimetric properties and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in patients with Huntington's disease (HD).

Methods: N = 39 motor-manifest HD patients, N = 74 Parkinson's disease (PD) patients and N = 92 matched HCs were administered the MoCA. HD patients further underwent the Unified Huntington's Disease Rating Scale (UHDRS), self-report questionnaires for anxiety and depression and a battery of first- and second-level cognitive tests.

Measuring cognitive impairment and monitoring cognitive decline in Huntington's disease: a comparison of assessment instruments.

Background: Progressive cognitive decline is an inevitable feature of Huntington's disease (HD) but specific criteria and instruments are still insufficiently developed to reliably classify patients into categories of cognitive severity and to monitor the progression of cognitive impairment.

Methods: We collected data from a cohort of 180 positive gene-carriers: 33 with premanifest HD and 147 with manifest HD. Using a specifically developed gold-standard for cognitive status we classified participants into those with normal cognition, those with mild cognitive impairment, and those with dementia.

The validation of the Italian version of multiple sclerosis neuropsychological screening questionnaire in Huntington's disease.

Introduction: Multiple sclerosis neuropsychological questionnaire (MSNQ) is a brief questionnaire useful for screening patient's and informant's self-perception of cognitive dysfunctions in daily life activities. Our study aims to evaluate the MSNQ validity in Huntington's disease (HD) mutation carriers and to correlate MSNQ scores with neurological, cognitive, and behavioral variables.

Methods: The study was conducted on a sample of 107 subjects from presymptomatic to the middle stage of HD recruited at LIRH Foundation and C.

Economic burden of Huntington disease in Europe and the USA: Results from the Huntington's Disease Burden of Illness study.

Background And Purpose: The prevalence of Huntington disease (HD) has increased over time; however, there is a lack of up-to-date evidence documenting the economic burden of HD by disease stage. This study provides an estimate of the annual direct medical, nonmedical, and indirect costs associated with HD from participants in the Huntington's Disease Burden of Illness (HDBOI) study in five European countries and the USA.

Methods: The HDBOI is a retrospective, cross-sectional study.

Semiology and determinants of apathy across neurodegenerative motor disorders: A comparison between amyotrophic lateral sclerosis, Parkinson's and Huntington's disease.

Background: The semiology and determinants of apathy are largely unknown across amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD), due to both motor and non-motor confounders. This study thus aimed at (1) profiling apathy in ALS, PD, and HD and (2) exploring its clinical determinants.

Materials: Consecutive ALS ( = 99), PD ( = 73), and HD ( = 25) patients underwent a motor-free assessment of apathy (Dimensional Apathy Scale, DAS), global cognition, anxiety and depression.

Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington's Disease.

Whether as a cause or a symptom, RNA transcription is recurrently altered in pathologic conditions. This is also true for non-coding RNAs, with regulatory functions in a variety of processes such as differentiation, cell identity and metabolism. In line with their increasingly recognized roles in cellular pathways, RNAs are also currently evaluated as possible disease biomarkers.

"Spazio Huntington": Tracing the Early Motor, Cognitive and Behavioral Profiles of Kids with Proven Pediatric Huntington Disease and Expanded Mutations > 80 CAG Repeats.

The "Spazio Huntington-A Place for Children" program was launched in 2019. The aim was to contact at risk kids within Huntington disease (HD) families, to provide counseling to their parents and to start a prospective follow-up of kids suspicious to manifest pediatric HD (PHD). We met 25 at risk kids in two years, four of whom with PHD and highly expanded (HE) mutations beyond 80 CAG repeats.

Cognitive Reserve in Early Manifest Huntington Disease Patients: Leisure Time Is Associated with Lower Cognitive and Functional Impairment.

We focused on Cognitive Reserve (CR) in patients with early Huntington Disease (HD) and investigated whether clinical outcomes might be influenced by lifetime intellectual enrichment over time. CR was evaluated by means of the Cognitive Reserve Index questionnaire (CRIq), an internationally validated scale which includes three sections: education, working activity, and leisure time. The clinical HD variables were quantified at three different time points (baseline-t0, 1 year follow up-t1 and 2 years follow up-t2) as per the Unified Huntington's Disease Rating Scale (UHDRS), an internationally standardized and validated scale including motor, cognitive, functional and behavioral assays.

Arithmetic Word-Problem Solving as Cognitive Marker of Progression in Pre-Manifest and Manifest Huntington's Disease.

Background: Arithmetic word-problem solving depends on the interaction of several cognitive processes that may be affected early in the disease in gene-mutation carriers for Huntington's disease (HD).

Objective: Our goal was to examine the pattern of performance of arithmetic tasks in premanifest and manifest HD, and to examine correlations between arithmetic task performance and other neuropsychological tasks.

Methods: We collected data from a multicenter cohort of 165 HD gene-mutation carriers.

Study Protocol for the Development of a European eHealth Platform to Improve Quality of Life in Individuals With Huntington's Disease and Their Partners (HD-eHelp Study): A User-Centered Design Approach.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that affects the quality of life (QoL) of HD gene expansion carriers (HDGECs) and their partners. Although HD expertise centers have been emerging across Europe, there are still some important barriers to care provision for those affected by this rare disease, including transportation costs, geographic distance of centers, and availability/accessibility of these services in general. eHealth seems promising in overcoming these barriers, yet research on eHealth in HD is limited and fails to use telehealth services specifically designed to fit the perspectives and expectations of HDGECs and their families.

Perceptions about Research Participation among Individuals at Risk and Individuals with Premanifest Huntington's Disease: A Survey Conducted by the European Huntington Association.

There has been great progress in Huntington's disease (HD) research. Yet, effective treatments to halt disease before the onset of disabling symptoms are still unavailable. Scientific breakthroughs require an active and lasting commitment from families.