View clinical trials related to Huntington Disease.
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Long-term follow-up of Huntington's disease patients treated with intrastriatal allografts is essential to assess the benefit/risk ratio of grafts as well as their effectiveness. Indeed, some patients are likely to develop adverse effects and the impact of alloimmunisation phenomena remains to be explored.
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.
Huntington's disease (HD) is a rare neurodegenerative condition caused by increased CAG trinucleotide repeats in the HTT gene, on chromosome 4. The estimated global prevalence is 2.71 cases per 100,000 inhabitants. In Brazil, it is estimated that 13,000 to 19,000 people carry the gene and 65,000 to 95,000 are descendants at risk. HD usually manifests itself in the fourth decade of life with motor, cognitive and behavioral symptoms, such as chorea. This condition profoundly affects quality of life and there is no treatment that can modify its course. Tetrabenazine is the only medication approved to control chorea. A partnership between the Butantan Institute and Cellavita investigates the use of Human Dental Pulp Stem Cells (hDPSCs) to treat HD. NestaCell® was developed, a product based on these cells, which express high levels of BDNF, an important neurotrophic factor for neuronal survival. Preclinical tests showed that NestaCell® is distributed to several organs, including the central nervous system, being well tolerated in toxicological tests in rats. In phase I (SAVE) and phase II (ADORE) clinical trials, NestaCell® was administered to patients with HD. The results indicated a significant improvement in motor scores and functional capacity compared to placebo, demonstrating a clinically significant benefit. NestaCell® also presented a good safety and tolerability profile, with few adverse events related to the product. The results support the conclusion that NestaCell® is safe and well tolerated in HD patients, within the doses tested.
Intro Huntington's disease (HD) patients suffer from motor, cognitive and behavioral impairments, with heterogeneous phenotypes and variable time course. This leads to a high variance of HD markers, none of which is currently sensitive enough to 1) measure disease progression from small cohort data, 2) predict disease entry in carriers of the HD mutation (during the prodromal phase or in patients considered asymptomatic: pre-HD patients), and 3) measure a significant evolution of the state of pre-HD patients over a time window compatible with the realization of clinical trials (about 2/3 years). Moreover, the markers of HD do not allow a fine stratification of the patients. Hypothesis/Objective Our objectives are 1) to evaluate the sensitivity of new markers and assessment tools for symptomatic (HD) and presymptomatic (pre-HD) patients, 2) to define a model of disease progression, and 3) to establish an enrichment strategy to improve patient selection for future therapeutic trials. Method We will evaluate newly developed cognitive tests, multimodal imaging techniques, biological markers and use innovative statistical approaches. We will follow 60 patients with the mutation responsible for MH (40 presymptomatic pre-MH patients, 20 symptomatic MH patients) and 20 healthy volunteers (controls) over a 24-month period.
NAC-preHD is a phase II randomized placebo controlled study of oral NAC among premanifest HD gene expansion carriers, with clinical and radiological outcome at three years.
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, both in the premanifest and manifest phase, 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.
Descriptive analysis of N- homocysteinylated Huntingtin in 3 groups of human fibroblasts: 1. presymptomatic HD individuals with UHDRS motor ≤ 5 (Mutated Huntingtin), 2. symptomatic HD individuals with motor UHDRS > 5 (Mutated Huntingtin) 3. human control cell lines, unmutated Huntingtin
Huntington's disease is a disabling neurodegenerative disease. Patients present with involuntary movements of the body and cognitive symptoms like behavioral problem, difficulty in planning tasks, etc. No effective treatment is currently available for them apart from symptomatic therapy. Currently, studies are going on the effectiveness of noninvasive brain stimulation (NIBS) in neurodegenerative diseases. It is a mode of brain stimulation technique where current is delivered into the brain by placing electrodes into their scalp. Transcranial pulsed current stimulation (tPCS) is a new modality of noninvasive brain stimulation. It is a device that generates electrical impulses. The current generated from this device can stimulate underlying brain areas. The investigators have planned to study the feasibility of non-invasive brain stimulation via tPCS in these patients of Huntington's disease. At first, the investigators will rate their involuntary body movement by a standard scale, assess arm movements by a robotic device, assess speech with standard protocol, assess brain electrophysiology by electroencephalography (EEG) and will also do gait (walking) analysis. Next, the investigators will give them 2 week (20 min/day) stimulation via real tPCS (active stimulation) or placebo (sham stimulation). After 2 weeks of stimulation, the investigators will re-assess the patient using the same tools mentioned pre-stimulation. Each patient will receive real and placebo stimulation with a 1-month gap in between. They will not know whether they are receiving real stimulation or placebo. Assessment will be done before stimulation, after 2 week real stimulation and after 2 week sham stimulation.
Huntington's disease often brings together 3 types of symptoms at one time or another of the disease during its evolution: motor, cognitive and psychiatric. Management requires comprehensive and multidisciplinary health, social or medico-social support. Its development generates additional difficulties for professionals who very often qualify this disease as "very complex" because it leads to a deep and severe impairment of physical and intellectual capacities. The sick person gradually loses their autonomy and becomes dependent for the acts of daily life, hence the choice of this disease for our study. Our study is focused on the quality of life at home of patients followed by the Angers Reference Center, "expert" on neurogenetic pathologies. Studies focusing on patients' quality of life at home have so far never been undertaken for a rare neurodegenerative disease like Huntington's disease.