Huntington Disease

The goal of this clinical trial is to test if the drug SKY-0515, an oral medication, can lower harmful proteins linked to Huntington's Disease (HD) and improve the symptoms of participants with HD. This study includes men and women aged 25 and older who have HD confirmed by genetic testing and meet certain requirements for physical ability and independence.

The goal of this first-in-human clinical trial is to assess the safety and tolerability of four doses of a new study drug called VO659 in people with genetic disorders called spinocerebellar ataxia type 1, type 3 or Huntington's disease. Another aim is to determine the concentrations of the study drug in the cerebral spinal fluid and blood after single and multiple doses. Study drug will be administered by lumbar intrathecal bolus injections.

MEND-HD is a longitudinal study evaluating the feasibility of passive monitoring of gait and chorea in patients with HD and the meaningfulness of these outcomes for patients with HD and their care partners/support persons. Participants will take part in four virtual visits with study investigators to answer survey questions on movement and cognition, perform in-home movement assessments, and take part in an interview regarding the meaningfulness of gait and chorea in their daily lives. Participant and care partner interviews will be used for symptom mapping and qualitative data analysis to assess the relevance and impact of the targeted symptoms on the participant's daily life. The study may be extended to 3 years to include yearly visits.

The purpose is to assess safety and tolerability of votoplam and to determine whether votoplam slows disease progression in patients with early symptomatic Huntington's disease (HD) compared to the control arm. HTT227 - current compound code (former code is PTC518 from PTC Therapeutics), HTT227 is Novartis code under Novartis sponsorship.

The goal of this clinical trial is to learn if pridopidine can slow the clinical decline of Huntington's Disease (HD) in adult participants. It will also inform about the safety of pridopidine. The main questions the study aims to answer are: Does pridopidine slow the overall worsening of HD over 1 year? Does pridopidine slow the worsening of specific aspects of HD over 1 year, namely the clinical progression, the ability to perform daily life activities (functional capacity), the mind's ability to process information (cognition), working of the muscles (motor function), and quality of life? Researchers will compare the drug pridopidine to a placebo (a look-alike substance that contains no drug) to see if pridopidine works better than placebo to treat HD. During the first year of the study, participants will have the same chance to receive either pridopidine or placebo. Participants will: Take 1 pridopidine or placebo capsule twice daily for 12 months. Visit the clinic 6 times within 1 year for checkups and tests. All participants who complete this 1-year placebo-controlled study period will roll over into an additional 2-year study period during which all participants will receive pridopidine treatment, including participants who had received placebo during the first year. During this additional 2-year treatment period participants will visit the clinic a total of 6 times for checkups and tests.

The main goal of this study is to evaluate the safety, tolerability, and preliminary efficacy of SPK-10001 in participants with Huntington's Disease.

The purpose of this research study is to determine the optimal pulse repetition frequency of low-intensity focused ultrasound that is safe and effective in improving motor symptoms in patients with Huntington's disease.

Cell-free fetal DNA (cffDNA) is present in the maternal blood from the early first trimester of gestation and makes up 5%-20% of the total circulating cell-free DNA (cfDNA) in maternal plasma. Its presence in maternal plasma has allowed development of noninvasive prenatal diagnosis for single-gene disorders (SGD-NIPD). This can be performed from 9 weeks of amenorrhea and offers an early, safe and accurate definitive diagnosis without the miscarriage risk associated with invasive procedures. One of the major difficulties is distinguishing fetal genotype in the high background of maternal cfDNA, which leads to several technical and analytical challenges. Besides, unlike noninvasive prenatal testing for aneuploidy, NIPD for monogenic diseases represent a smaller market opportunity, and many cases must be provided on a bespoke, patient- or disease-specific basis. As a result, implementation of SGD-NIPD remained sparse, with most testing being delivered in a research setting. The present project aims to take advantage of the unique French collaborative network to make SGD-NIPD possible for theoretically any monogenic disorder and any family.

The purpose of this research study is to determine whether an implantation of hNSC-01 is a safe and tolerable study intervention for Huntington's disease. This study is the first time that hNSC-01 is being tested in people.

This is a phase 1, single-center, single-dose, open-label mass-balance study to evaluate radioactive recovery rate, radioactive PK characteristics, metabolite identification, and to observe the safety in healthy male subjects of \[14C\] LPM3770164.

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by progressively worsening motor, cognitive, psychiatric, and behavioral deficits. Cognitive deficits occur early on, affecting in particular executive functions (inhibition, flexibility), decision-making, memory, attention (selective, sustained), perceptual and visuospatial skills, and information processing speed. More specifically, memory deficits quickly affect different memory systems (short-term memory, long-term memory, etc.), including autobiographical memory. Autobiographical memory is usually defined as a system that stores all the information (semantic component) and specific memories (episodic component) specific to an individual, accumulated from an early age. Autobiographical memory is now considered essential to the construction of a sense of identity and continuity. It is also considered indispensable for projecting into the future, otherwise known as "episodic future thinking," a fundamental human capacity that is both anticipatory and adaptive. Autobiographical memory deficits remain largely unexplored in HD, with only three studies identified in the international literature on the subject, one of which is actually based on the same neuropsychological data as another, adding a neuroanatomical analysis focused on autobiographical memory. These studies show that the autobiographical recollections of patients with HD are mainly descriptive recollections of personal events lacking in detail, and that the abnormalities appear to be linked to the progressive degeneration of a vast cortico-subcortical brain network comprising the medial temporal cortex, the frontal cortex, and the posterior striatal and parietal regions. Deficits in episodic future thinking have never been explored in HD. A better understanding of the mechanisms underlying this type of cognitive impairment (recalling personal memories and mentally simulating future personal events) remains a major challenge today in improving the care of patients with HD. Several recent studies have shown, in different pathological contexts (Alzheimer's disease, etc.), that the parallel use of neuropsychological tests (tasks and questionnaires) and an eye-tracking system allows for a much more accurate and in-depth examination of cognitive functions (for a review, see). In addition, eye movements, such as fixations and saccades, have been associated with the retrieval of autobiographical events . These movements better reflected the person's subjective experience, particularly with regard to the visual elements of mental imagery of recovered events. This suggests that the analysis of eye behavior could enrich the assessment of autobiographical memory, beyond the data provided by traditional tests. The examination of eye movements is therefore, alongside neuropsychological testing, a promising non-invasive method for better understanding the characteristics of autobiographical memory in HD. This project therefore aims to explore the autobiographical memory of HD patients by analyzing their eye activity during tasks involving the recall of personal events using standard neuropsychological tools. By identifying oculomotor markers associated with autobiographical memory disorders, this research could: (1) provide a better understanding of the neurocognitive profile of HD, (2) pave the way for more accurate diagnostic tools, and (3) form an important basis for the development of future interventions aimed at supporting memory function in this population.

This is a FIH (first-in-human) study to evaluate the clinical utility of the radioligand \[11C\]CHDI-00491009 as a PET tracer that binds specifically to mutant huntingtin (mHTT) aggregates in Huntington's disease (HD). The study is divided into three cohorts defined by the Huntington's Disease Integrated Staging System (HD-ISS): Cohort 1 - initial tracer validation (3 healthy controls (HCs)); Cohort 2 - target validation and test-retest variability (6 HD-ISS Stage 3 participants and 6 age and biological sex-matched HCs); Cohort 3 - target sensitivity (6 HD-ISS Stage 2 participants and 6 age and biological sex-matched HCs). An interim analysis (IA) will be conducted after the completion of each cohort, followed by a final analysis for the study. In addition to imaging, exploratory biomarkers, including somatic instability index, soluble mHTT and total huntingtin (HTT), will be assessed. All participants with HD (PwHD) will have an additional blood sample drawn at the screening visit to assess the somatic instability index and will also be invited to provide an optional cerebrospinal fluid (CSF) sample for measurement of soluble mHTT and total HTT.

The goal of this observational study is to learn about the usefulness of a test of social functioning in persons with Huntington disease. Huntington disease affects motor function, psychological well-being and cognitive functions ("thinking abilities" such as paying attention, remembering and solving problems). It is also believed to affect important social functions, including the ability to understand others' intentions and emotions (social cognition). The test of interest in this study is called The Double Movie for the Assessment of Social Cognition-Multiple Choice (DMASC-MC) and will be compared to two other similar and well-known tests. The main question which the study aims to answer is: • Is DMASC-MC a useful tool for detecting problems with social functioning in adult persons with early Huntington disease? In the study, participants will meet with a medical doctor and a psychologist for assessment of different symptoms related to Huntington disease, including social functioning. Better methods for identifying problems with social functioning could help persons with Huntington disease and their families in mainly two ways. Firstly, it could increase their understanding of how the disease has affected them. Secondly, a better understanding of these problems could lead to better recommendations and interventions from medical teams, which would also benefit persons with Huntington disease and families.

The purpose of the current proposal is to expand understanding of two currently available cognitive tools that are not typically used in Huntington Disease (HD) clinical trials that might be useful both for initial screening and for clinical trial application. One is the Coding Test and the other is the Self-Administered Gerocognitive Examination (SAGE). Both the Coding Test and the SAGE have been used for assessments of individuals with other neurodegenerative diseases, including Alzheimer's Disease, Parkinson's Disease and Lewy Body Disease, but data is lacking on their use in individuals with HD.

Huntington disease (HD, 1.3/10 000) is an autosomal dominant disease due to an abnormal expansion of CAG triplets in HTT gene. Several pathophysiological mechanisms have been evoked, including an alteration of the signaling pathway of the Brain Derived Neurotrophic Factor (BDNF), a neurotrophic factor involved in the survival of neurons (striatal and hippocampal) and synaptic plasticity. BDNF is synthesized at the level of cortical neurons and transported, through the axonal transport in which the Htt is involved, to the nerve endings; it's then secreted in response to excitatory synaptic activity, especially at the level of glutamatergic synapses. Besides, at the postsynaptic level it binds with great specificity to TrkB receptors (tropomyosin-related kinase receptors B) with a neuroprotective effect on dendritic and axonal growth and an increase in synaptic plasticity, especially at the level of the striatum and the hippocampus. BDNF is decreased in the brain of animal models, as well as in patients with HD; the alteration of this pathway would occur in the early stages of the disease. In the context of concomitant multiple treatments, the BNDF pathway may be one of the therapeutic targets of HD. Moreover, in HD it remains essential to detect biological markers representative of the different pathogenic pathways that can be tested in vivo in humans to confirm the hypotheses developed at the level of basic research; these biomarkers could subsequently become biomarkers of disease progression and/or biomarkers of therapeutic efficacy of potential targeted treatments. Therefore, this study aims to characterize potential biomarkers of the BNDF pathway in plasma and CSF in subjects with HD and to confirm the importance of this pathogenic mechanism in vivo in humans.

The researchers hope to find out effects of transcranial direct current stimulation (tDCS) sessions on the behavioral symptoms of Huntington's Disease. If participants are eligible to continue, they will be provided a device to administer the tDCS for 30 minutes each day and be asked to answer questions with the study staff . Participants will be asked to return to the study center for follow ups and to undergo additional cognitive tests and questionnaires. Participants will also be asked to answer questionnaires via a web conferencing platform (Zoom) during the course of the study. Caregivers of the participants will be asked to answer questionnaires to collect more information about the participants.

The purpose of this study is to assess feasibility, acceptability, and safety of providing transcranial direct current stimulation( tDCS) to Huntingtons Disease (HD) patients in the early to middle stages and to assess the efficacy of tDCS for HD-related behavioral, cognitive and other symptoms

This study aims to develop and evaluate biomarkers using non-invasive optical coherence tomography (OCT) and OCT angiography (OCTA) as well as ultra-widefield (UWF) fundus photography to assess the structure and function of the retinal and choroidal microvasculature and structure in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), Parkinson's Disease (PD), or other neurodegenerative disease, diseases as outlined.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, characterized by movement disorders, behavioural disorders and cognitive decline. Especially the behavioural and cognitive symptoms of the disease lead to significant disability and burden for patients as well as caregivers. One of the cognitive domains affected by HD is social cognition. Social cognition is the ability to perceive, interpret and respond correctly to social information. Aspects of social cognition are emotion recognition, perspective taking (Theory of Mind), and emapathy. Social cognition problems can be related to behavioural problems, but to be able to study this relationship, it is important to be able to reliable measure social cognition impairments. There are a few social cognition tests available, but often they are not normd and validated for use in a Dutch neurological population. There is a lack of sensitive, simple, tests for measuring Theory of Mind in patients with HD. A promising test, that already has been proven valid in a psychiatric population, is the Hinting Task. The Hinting Task measures theory of mind through indirect speech, The Hinting task is a social cognition test, where hints are implicitly given in speech, which resembles what patients and caregivers frequently report as difficult in HD. The Hinting Task has already been translated into Dutch and is already being used in clinical parctice, but its sensitivity has not been studied yet in a neurological population. The aim of this study is to assess if the Hinting Task is sensitive in patients with HD and to relate the Hinting Task to other (social) cognitive measures, demographical characteristics and disease characteristics.

The objective of the study is to validate the use of wearable sensors and digital health technologies for monitoring disease activity in Huntington's Disease (HD). Healthy subjects, as well as subjects with documented diagnosis of HD will be screened and recruited at University of Rochester Medical Center and Vanderbilt University Medical Center to participate in this 12-month observational study. There will be a total of 5 visits every approximately 3 months. In each study visit, participants will complete several Patient Reported Outcomes (PROs), Clinical Reported Outcomes, complete a series of Digital Assessments (Speech, Cognitive, Motor, and Finger Tapping). Participants will be provided with a pendant, wrist, and ankle sensors to monitor their daily physical activities for 7 days after each study visit. Participants will also be provided with a tablet to complete digital assessments (Speech, Cognitive, Motor, and Finger Tapping) on monthly basis at home.

The study is an open-label clinical trial evaluating whether music therapy combined with conventional management reduces irritability and impulsivity in 15 patients with early-stage Huntington's disease. This pilot study aims to show the interest of alternative non-pharmacological measures such as a digital music therapy tool, adapted to an audience of Huntington's patients, to help manage the psychobehavioral symptoms frequently observed in this affection, and to avoid breakdowns due to caregiver exhaustion.

LEAD-HD is intended to collect and analyze self-reported health information from individuals with Huntington Disease (HD) or prodromal HD participating in a 24-month longitudinal natural history study using remote technologies.

The ActiLiège-Adult study is a prospective, longitudinal, observational study designed to collect natural history data on adult patients with neurological or metabolic diseases affecting movement. Conducted at the Centre de Référence Liégeois des Maladies Neuromusculaires in Liège, Belgium, the study will enroll 300 ambulant patients, including individuals with neuromuscular disorders and obesity. Using the Syde® wearable device, the study aims to continuously monitor motor function in real-life settings over a period of up to two years. The primary objective is to evaluate the utility of digital mobility outcomes, such as the 95th centile of stride velocity (SV95C), as reliable and objective endpoints for future clinical trials.

Positron Emission Tomography (PET) is a functional imaging technique, which enables in vivo visualization of biological molecules expressed in human tissues. Brain PET is most powerful to study a vast range of neurological and psychiatric disorders in vivo, targeting neuronal and glial activity, metabolism, cerebral blood flow, receptor proteins or misfolded proteins. In vivo imaging of synaptic density in the human brain has become feasible through development of \[11C\]UCB-J, a PET radioligand for the synaptic vesicle protein SV2A, which is ubiquitously and homogeneously present in presynaptic terminals throughout the brain. A first study in Huntington's disease (HD) mutation carriers showed loss of striatal \[11C\]UCB-J binding (also when corrected for atrophy), as well as in the neocortex (Delva et al, Neurology 2022). Moreover, regional synaptic loss was highly correlated to motor impairment. In order to be able to use SV2A PET as widespread available biomarker tool to assess synaptic integrity, disease progression and/or response to mHTT lowering drugs, the short half-life of 11C (20 minutes) for \[11C\]UCB-J remains a hurdle. Recently, \[18F\]SynVesT-1, an optimized 18F-labeled analogue of \[11C\]UCB-J with similar kinetics, binding affinity, and test-retest precision properties has been evaluated in humans. However, there is evidence from preclinical studies conducted at University of Antwerp that in the zQ175DN knock-in mouse model of HD, larger variability and lower effect-sizes are seen with \[18F\]SynVest-1 than with \[11C\]UCB-J. In order to ascertain a similar effect size and quantification properties for \[18F\]SynVest-1 and \[11C\]UCB-J PET in human HD patients and to validate simplified measures (such as SUVR with white matter as reference region) and SynVest, this head-to-head fully quantitative study is performed.

The purpose of this study is to find out if there is a connection between the naturally occurring bacteria in our bodies and the progression of Huntington disease. The investigators are trying to determine if patients who are diagnosed with adult-onset HD and who exhibit a rapid rate of disease progression have unique populations of bacteria in their gut as compared to patients with slower progression.