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Lee, Jee-Young,Jeon, Beom Seok Korean Movement Disorders Society 2014 Journal of movement disorders: official journal of Vol.7 No.2
<P>Impulse control disorders (ICD) in Parkinson’s disease (PD) are a disabling non-motor symptom with frequencies of 13–35% among patients receiving dopamine replacement therapy. ICD in PD is strongly associated with dopaminergic drug use, especially non-ergot dopamine agonists (DA). However, individual susceptibility and disease-related neural changes are also important contributors to the development of ICD. Discrepancies between nigrostriatal and mesolimbic dopaminergic degeneration and non-physiological administration of dopaminergic drugs may induce abnormal ’hyperstimulation’ of the mesolimbic system, which alters reward-learning behaviors in PD patients. In addition, DA can make patients more impulsive during decision-making and seek risk-taking behaviors. DA intake is also related to the biased representation of rewards. Ultimately, loss of negative feedback control due to dysfunctional frontostriatal connections is necessary for the establishment of ICD in PD. The subsequent behavioral and neural changes are affected by PD treatment and disease progression; thus, proper treatment guidelines for physicians are needed to prevent the development of ICD. Future studies aimed at producing novel therapeutics to control the risk factors for ICD or treat ICD behaviors in PD are warranted. This review summarizes recent advances from epidemiological and pathophysiological studies on ICD in PD. Management principles and limitations of current therapeutics are briefly discussed.</P>
Applications of CRISPR/Cas9 for Gene Editing in Hereditary Movement Disorders
Im, Wooseok,Moon, Jangsup,Kim, Manho The Korean Movement Disorder Society 2016 Journal of movement disorders: official journal of Vol.9 No.3
<P>Gene therapy is a potential therapeutic strategy for treating hereditary movement disorders, including hereditary ataxia, dystonia, Huntington’s disease, and Parkinson’s disease. Genome editing is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome using modified nucleases. Recently, clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 (CRISPR/Cas9) has been used as an essential tool in biotechnology. Cas9 is an RNA-guided DNA endonuclease enzyme that was originally associated with the adaptive immune system of <I>Streptococcus pyogenes</I> and is now being utilized as a genome editing tool to induce double strand breaks in DNA. CRISPR/Cas9 has advantages in terms of clinical applicability over other genome editing technologies such as zinc-finger nucleases and transcription activator-like effector nucleases because of easy <I>in vivo</I> delivery. Here, we review and discuss the applicability of CRISPR/Cas9 to preclinical studies or gene therapy in hereditary movement disorders.</P>
Ahn, Jong Hyeon,Kim, Ah Reum,Kim, Nayoung K. D.,Park, Woong-Yang,Kim, Ji Sun,Kim, Minkyeong,Park, Jongkyu,Lee, Jung-Il,Cho, Jin Whan,Cho, Kyung Rae,Youn, Jinyoung The Korean Movement Disorder Society 2019 Journal of movement disorders: official journal of Vol.12 No.2
<P><B>Objective</B></P><P>The aim of this study was to investigate the efficacy of globus pallidus interna deep brain stimulation (GPi-DBS) for treating dystonia due to the <I>GNAL</I> mutation.</P><P><B>Methods</B></P><P>We provide the first report of a dystonia patient with a genetically confirmed <I>GNAL</I> mutation in the Korean population and reviewed the literature on patients with the <I>GNAL</I> mutation who underwent GPi-DBS. We compared the effectiveness of DBS in patients with the <I>GNAL</I> mutation compared to that in patients with DYT1 and DYT6 in a previous study.</P><P><B>Results</B></P><P>Patients with the <I>GNAL</I> mutation and those with DYT1 had higher early responder rates (<I>GNAL</I>, 5/5, 100%; DYT1, 7/7, 100%) than did patients with DYT6 (<I>p</I> = 0.047). The responder rates at late follow-up did not differ statistically among the three groups (<I>p</I> = 0.278). The decrease in the dystonia motor scale score in the <I>GNAL</I> group was 46.9% at early follow-up and 63.4% at late follow-up.</P><P><B>Conclusion</B></P><P>GPi-DBS would be an effective treatment option for dystonia patients with the <I>GNAL</I> mutation who are resistant to medication or botulinum toxin treatment.</P>
Exosome-Based Delivery of miR-124 in a Huntington’s Disease Model
Lee, Soon-Tae,Im, Wooseok,Ban, Jae-Jun,Lee, Mijung,Jung, Keun-Hwa,Lee, Sang Kun,Chu, Kon,Kim, Manho The Korean Movement Disorder Society 2017 Journal of movement disorders: official journal of Vol.10 No.1
<P><B>Objective </B></P><P>Huntington’s disease (HD) is a genetic neurodegenerative disease that is caused by abnormal CAG expansion. Altered microRNA (miRNA) expression also causes abnormal gene regulation in this neurodegenerative disease. The delivery of abnormally downregulated miRNAs might restore normal gene regulation and have a therapeutic effect. </P><P><B>Methods </B></P><P>We developed an exosome-based delivery method to treat this neurodegenerative disease. miR-124, one of the key miRNAs that is repressed in HD, was stably overexpressed in a stable cell line. Exosomes were then harvested from these cells using an optimized protocol. The exosomes (Exo-124) exhibited a high level of miR-124 expression and were taken up by recipient cells. </P><P><B>Results </B></P><P>When Exo-124 was injected into the striatum of R6/2 transgenic HD mice, expression of the target gene, RE1-Silencing Transcription Factor, was reduced. However, Exo-124 treatment did not produce significant behavioral improvement. </P><P><B>Conclusion </B></P><P>This study serves as a proof of concept for exosome-based delivery of miRNA in neurodegenerative diseases.</P>
Mechanism of Anti-α-Synuclein Immunotherapy
Lee, Jun Sung,Lee, Seung-Jae The Korean Movement Disorders Society 2016 Journal of movement disorders: official journal of Vol.9 No.1
<P>Immunization therapy targeting α-synuclein has emerged as a promising approach for Parkinson’s disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that α-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular α-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of α-synuclein immunotherapy. </P>
Episodic Ataxias: Clinical and Genetic Features
Choi, Kwang-Dong,Choi, Jae-Hwan The Korean Movement Disorder Society 2016 Journal of movement disorders: official journal of Vol.9 No.3
<P>Episodic ataxia (EA) is a clinically heterogeneous group of disorders that are characterized by recurrent spells of truncal ataxia and incoordination lasting minutes to hours. Most have an autosomal dominant inheritance pattern. To date, 8 subtypes have been defined according to clinical and genetic characteristics, and five genes are known to be linked to EAs. Both EA1 and EA2, which are caused by mutations in <I>KCNA1</I> and <I>CACNA1A</I>, account for the majority of EA, but many patients with no identified mutations still exhibit EA-like clinical features. Furthermore, genetically confirmed EAs have mostly been identified in Caucasian families. In this article, we review the current knowledge on the clinical and genetic characteristics of EAs. Additionally, we summarize the phenotypic features of the genetically confirmed EA2 families in Korea.</P>
Park, Kye Won,Ryu, Ho-Sung,Kim, Juyeon,Chung, Sun Ju The Korean Movement Disorder Society 2017 Journal of movement disorders: official journal of Vol.10 No.3
<P>Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant inherited disease caused by mutations of the human gap junction alpha 1 gene, which encodes the protein Connexin-43. Patients with ODDD may present with neurological deficits with a typical pleiotropic combination of characteristic craniofacial, ophthalmological, phalangeal, and dental anomalies. In this report, we describe the first genetically confirmed Korean ODDD patient, who presented with spastic paraparesis. We will also review the neurological aspects of ODDD as reported in the literature.</P>
Ryu, Ho-Sung,Kim, Mi-Sun,You, Sooyeoun,Kim, Mi-Jung,Kim, Young Jin,Kim, Juyeon,Kim, Kiju,Chung, Sun Ju The Korean Movement Disorder Society 2017 Journal of movement disorders: official journal of Vol.10 No.2
<P><B>Objective</B></P><P>To compare the therapeutic and adverse effects of globus pallidus interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of advanced Parkinson’s disease (PD).</P><P><B>Methods</B></P><P>We retrospectively analyzed the clinical data of patients with PD who underwent GPi (<I>n</I> = 14) or STN (<I>n</I> = 28) DBS surgery between April 2002 and May 2014. The subjects were matched for age at surgery and disease duration. The Unified Parkinson’s Disease Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) at baseline and 12 months after surgery were used to assess the therapeutic effects of DBS. Adverse effects were also compared between the two groups.</P><P><B>Results</B></P><P>At 12 months, the mean changes in the UPDRS total and part I–IV scores did not differ significantly between the two groups. However, the subscores for gait disturbance/postural instability and dyskinesia were significantly more improved after GPi DBS than those after STN DBS (<I>p</I> = 0.024 and 0.016, respectively). The LED was significantly more reduced in patients after STN DBS than that after GPi DBS (<I>p</I> = 0.004). Serious adverse effects did not differ between the two groups (<I>p</I> = 0.697).</P><P><B>Conclusion</B></P><P>The patients with PD showed greater improvement in gait disturbance/postural instability and dyskinesia after GPi DBS compared with those after STN DBS, although the patients had a greater reduction in LED after STN DBS. These results may provide useful information for optimal target selection for DBS in PD.</P>