更新于：2024-04-01
Huntington Disease
亨廷顿舞蹈病
更新于：2024-04-01
基本信息
别名 Akinetic Rigid Variant of Huntington Disease、Akinetic-Rigid Variant of Huntington Disease、CHOREA, CHRONIC PROGRESSIVE HEREDITARY + [76] |
简介 A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4) |
关联
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原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
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靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
Phase III Efficacy and Safety of NestaCell® in Moderated Huntington's Disease
Evaluation of the Diagnostic Performance of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
Direct Quantitative Comparison Between [11C]UCB-J and [18F]SynVest-1 PET as Markers for Synaptic Density in Premanifest and Manifest Huntington's Disease.
100 项与 亨廷顿舞蹈病 相关的临床结果
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100 项与 亨廷顿舞蹈病 相关的转化医学
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2024-09-01Neural regeneration research
Therapeutic advances in neural regeneration for Huntington's disease.
Article
作者: Francesco D'Egidio ; Vanessa Castelli ; Giorgia Lombardozzi ; Fabrizio Ammannito ; Annamaria Cimini ; Michele d'Angelo
Huntington's disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington's disease. From a clinical point of view, Huntington's disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington's disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington's disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington's disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington's disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, numerous have been the attempts in several preclinical models of Huntington's disease to evaluate the feasibility of invasive and non-invasive approaches. Thus, the aim of this review is to offer an overview of the most appealing approaches spanning from stem cell-based cell therapy to extracellular vesicles such as exosomes in light of promoting neurogenesis, discussing the results obtained so far, their limits and the future perspectives regarding the neural regeneration in the context of Huntington's disease.
2024-07-01Neural regeneration research
Neuronal conversion from glia to replenish the lost neurons.
Article
作者: Shiyu Liang ; Jing Zhou ; Xiaolin Yu ; Shuai Lu ; Ruitian Liu
ABSTRACT:
Neuronal injury, aging, and cerebrovascular and neurodegenerative diseases such as cerebral infarction, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Huntington's disease are characterized by significant neuronal loss. Unfortunately, the neurons of most mammals including humans do not possess the ability to self-regenerate. Replenishment of lost neurons becomes an appealing therapeutic strategy to reverse the disease phenotype. Transplantation of pluripotent neural stem cells can supplement the missing neurons in the brain, but it carries the risk of causing gene mutation, tumorigenesis, severe inflammation, and obstructive hydrocephalus induced by brain edema. Conversion of neural or non-neural lineage cells into functional neurons is a promising strategy for the diseases involving neuron loss, which may overcome the above-mentioned disadvantages of neural stem cell therapy. Thus far, many strategies to transform astrocytes, fibroblasts, microglia, Müller glia, NG2 cells, and other glial cells to mature and functional neurons, or for the conversion between neuronal subtypes have been developed through the regulation of transcription factors, polypyrimidine tract binding protein 1 (PTBP1), and small chemical molecules or are based on a combination of several factors and the location in the central nervous system. However, some recent papers did not obtain expected results, and discrepancies exist. Therefore, in this review, we discuss the history of neuronal transdifferentiation, summarize the strategies for neuronal replenishment and conversion from glia, especially astrocytes, and point out that biosafety, new strategies, and the accurate origin of the truly converted neurons in vivo should be focused upon in future studies. It also arises the attention of replenishing the lost neurons from glia by gene therapies such as up-regulation of some transcription factors or down-regulation of PTBP1 or drug interference therapies.
2024-06-30Acta neurologica Taiwanica
Treatment of Intracranial Hemorrhage Induced Hemichorea- Hemiballism by Low-Frequency Repetitive Transcranial Magnetic Stimulation.
Article
作者: Yuka Nakaya ; Koji Hayashi ; Asuka Suzuki ; Rei Asano ; Kouji Hayashi ; Kazuki Fujita ; Kaori Kawabata ; Yasutaka Kobayashi ; Mamiko Sato
An 80-year-old woman with a history of rheumatoid arthritis, hypertension, and hyperlipidemia, and no family history of hyperkinesis developed suddenly involuntary movement and visited our hospital two-day after onset. Neuro-examination revealed hemichorea-hemiballismus in the right side of the body, including the face (Suppl. video). Blood tests revealed neither hyperglycemia nor acanthocyte. Brain MRI showed acute microbleeding in the left subthalamic nucleus (Figure 1A-C). Although she was treated with haloperidol (max. 4.5 mg/day), hemichorea-hemiballismus did not subside. Repetitive transcranial magnetic stimulation (rTMS) with a low-frequency protocol (LFP) (1 Hz, 1200 pulses, with a stimulus intensity of 90% of the resting motor threshold, 3 days/week for 2-week) was applied to the left precentral knob (Figure 1D). Its effect was drastic, as the symptoms disappeared for half-hour after rTMS. Hemichorea-hemiballism then reappeared but was attenuated by repeated rTMS. The symptoms disappeared after one-month. Subthalamic nucleus lesions can develop hemichorea-hemiballism (1). According to a study on Huntington's disease and diabetic hemichorea-hemiballism, increased thalamocortical drive may increase the excitability of excitatory and inhibitory circuits of the frontal cortex as the etiologies of hyperkinesia (2-3). However, the target points of rTMS in treating hemichorea-hemiballism have not been consistent in literature. Moreover, rTMS with a LFP on the bilateral supplementary motor areas is effective in treating chorea in Huntington's disease (2). Additionally, rTMS on the ipsilateral precentral knob (primary motor cortex) with continuous θ burst stimulation (cTBS), which decreases the excitability and inhibitory cortical circuits, was effective in treating contralateral hemichorea caused by midbrain hemorrhage (3). Similar to cTBS, LFP can suppress cortical excitation (4); therefore, we applied rTMS with LFP on the primary motor cortex to treat hemichorea-hemiballism. Our results were drastic for both short- and long-term efficiency. This is the first report of the efficacy of rTMS with LFP in treating hemichorea-hemiballism caused by encephalorrhagia.
2024-03-30
2024-03-28
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