{"title":"Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson's Disease.","authors":"Seong Ho Jeong, Phil Hyu Lee","doi":"10.14802/jmd.25008","DOIUrl":"https://doi.org/10.14802/jmd.25008","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and non-dopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer a promising approach to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spastic paraplegia 82 in two Asian Indian siblings with PCYT2 mutation.","authors":"Anil Dash, Farsana Mustafa, Divyani Garg, Sreeja Samineni, Ayush Agarwal, Ajay Garg, Achal Kumar Srivastava","doi":"10.14802/jmd.24259","DOIUrl":"https://doi.org/10.14802/jmd.24259","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnosing Cerebrotendinous Xanthomatosis in a Middle-Aged Woman with Cervical Dystonia.","authors":"Wei-Sheng Wang, Yu-Ping Chiu, Meng-Han Tsai, Shey-Lin Wu, Yen-Chung Chen","doi":"10.14802/jmd.24202","DOIUrl":"https://doi.org/10.14802/jmd.24202","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Levodopa Pharmacokinetics in Switching from Levodopa/Carbidopa Intestinal Gel to Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion in a Patient with Parkinson's Disease: a case report.","authors":"Tomonori Nukariya, Toshiki Tezuka, Shohei Okusa, Ryotaro Okochi, Yuto Sakai, Yoshihiro Nihei, Jin Nakahara, Morinobu Seki","doi":"10.14802/jmd.24247","DOIUrl":"https://doi.org/10.14802/jmd.24247","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pre-DBS modified Tremor/Postural instability and gait difficulty score ratio as indicator of short-term outcome of subthalamic nucleus DBS in Parkinson's disease.","authors":"Chakradhar Reddy, Kanchana Pillai, Shejoy Joshua, Anup Nair, Harshad Chavotiya, Manas Chacko, Asha Kishore","doi":"10.14802/jmd.24175","DOIUrl":"https://doi.org/10.14802/jmd.24175","url":null,"abstract":"<p><strong>Purpose: </strong>The outcomes of motor and non-motor features of Parkinson's disease (PD) following DBS vary among its subtypes. We tested whether pre-operative motor subtyping using the modified Tremor/PIGD ratio, could indicate the short-term motor, non-motor and quality of life (QOL) outcomes of STN-DBS.</p><p><strong>Method: </strong>In this prospective study, 39 consecutive STN-DBS cases were assessed in Drug-OFF state before surgery and subtyped using the ratio of tremor and PIGD scores (T/P ratio). 6 months after surgery patients were reassessed in Stimulation ON-Drug OFF state and the percentage change in motor, non-motor and QOL scores (PDQ39) was calculated.</p><p><strong>Results: </strong>The modified T/P ratio had a moderate, positive correlation with the percentage change in scores of UPDRS III in OFF, sum of cardinal motor signs, non-motor symptoms scale (NMSS) and quality of life (PDQ39).</p><p><strong>Conclusion: </strong>Preoperative PD motor subtyping can be used as an indicator of the short-term, outcomes of STN-DBS in PD.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kruzette Khloe L Solijon, Sheina B Magtuba, Noel Belonguel, Gerard Saranza
{"title":"Myoclonic Epilepsy of Unverricht and Lundborg in a Filipino Woman.","authors":"Kruzette Khloe L Solijon, Sheina B Magtuba, Noel Belonguel, Gerard Saranza","doi":"10.14802/jmd.24172","DOIUrl":"10.14802/jmd.24172","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":"96-98"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Han-Kyeol Kim, Sung-Woo Kim, Jin Yong Hong, Min Seok Baek
{"title":"Gait Parameters in Healthy Older Adults in Korea.","authors":"Han-Kyeol Kim, Sung-Woo Kim, Jin Yong Hong, Min Seok Baek","doi":"10.14802/jmd.24181","DOIUrl":"10.14802/jmd.24181","url":null,"abstract":"<p><strong>Objective: </strong>Gaits constitute the most fundamental and common form of human locomotion and are essential in daily activities. We aimed to investigate gait parameters in medically and cognitively healthy older adults to determine the independent effects of age, physical attributes, and cognition on these parameters.</p><p><strong>Methods: </strong>This retrospective study enrolled healthy older adult participants aged 50 years or older with normal cognition and no neurological symptoms or medical/surgical history that could affect gait. Quantitative gait analysis was conducted via the GAITRite Electronic Walkway, which categorizes gait parameters into spatiotemporal, spatial, temporal, phase, and variability. Gait parameters were compared between sexes across different age groups. The independent effects of age, Mini-Mental State Examination score, and physical characteristics were analyzed via a multiple regression model.</p><p><strong>Results: </strong>This study included 184 participants with an average age of 72.2 years. After adjusting for age, height, and footwear, only the base width and its variability differed between the sexes. Gait parameters varied significantly among different age groups, revealing multiple interparameter associations. Age was independently correlated with decreased velocity, step and stride lengths, single support time percentage and increased double support time, double support time percentage, and variability parameters, excluding the coefficient of variance of base width. Height was positively correlated with velocity, step and stride lengths, and base width, whereas leg length was negatively associated with cadence and positively associated with temporal parameters of gait.</p><p><strong>Conclusion: </strong>Gait parameters in healthy older adults were not only associated with age and physical characteristics but also had interparameter correlations.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":"55-64"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lina Okar, Peyton Murin, Anagha Prabhune, Richard Bucholz, Pratap Chand
{"title":"The Application of Deep Brain Stimulation in the Syndrome of Irreversible Lithium-Effectuated Neurotoxicity.","authors":"Lina Okar, Peyton Murin, Anagha Prabhune, Richard Bucholz, Pratap Chand","doi":"10.14802/jmd.24209","DOIUrl":"10.14802/jmd.24209","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":"101-102"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Video-Oculography for Enhancing the Diagnostic Accuracy of Early Oculomotor Dysfunction in Progressive Supranuclear Palsy.","authors":"Harshad Chovatiya, Kanchana Pillai, Chakradhar Reddy, Amiya Thalakkattu, Ayana Avarachan, Manas Chacko, Asha Kishore","doi":"10.14802/jmd.24171","DOIUrl":"10.14802/jmd.24171","url":null,"abstract":"<p><strong>Objective: </strong>Oculomotor impairment is an important diagnostic feature of progressive supranuclear palsy (PSP) and PSP subtypes. We assessed the role of video-oculography (VOG) in confirming clinically suspected slow saccades in PSP and differentiating PSP from Parkinson's disease (PD). We also measured the correlation of both saccadic velocity and latency in PSP patients with scores on the PSP Rating Scale, Montreal Cognitive Assessment, and frontal assessment battery. We assessed the frequency of apraxia of eyelid opening (ALO) and reflex blepharospasm in PSP and PD patients.</p><p><strong>Methods: </strong>A total of 112 PSP patients with slow saccades but not gaze palsy, 50 PD patients, and 50 healthy controls (HCs) were recruited. The Movement Disorders Society task force-PSP and PD criteria were used for the diagnoses. All the subjects underwent VOG.</p><p><strong>Results: </strong>Horizontal and vertical saccadic velocities and latencies differentiated PSP patients from PD patients and HCs (p<0.001). Vertical saccadic velocity and latency accurately differentiated PSP with predominant parkinsonism (PSP-P) patients from PD patients (p<0.001 and 0.012, respectively). A couple of vertical and horizontal saccadic velocities differentiated PSP-Richardson's syndrome (PSP-RS) patients from PSP-P patients (vertical velocity of left eye: p=0.024; horizontal velocity of right eye: p=0.030). In vertical gaze, the mean velocity cutoff showed good sensitivity and specificity in differentiating PSP patients from HCs and PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse global cognitive and frontal dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.</p><p><strong>Conclusion: </strong>VOG is useful for confirming slow saccades in PSP-RS and PSP-P patients and for differentiating PSP-P patients from PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse cognitive dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":"77-86"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Whan Cho, Jee-Young Lee, Han-Joon Kim, Joong-Seok Kim, Kun-Woo Park, Seong-Min Choi, Chul Hyoung Lyoo, Seong-Beom Koh
{"title":"Efficacy and Safety of Taltirelin Hydrate in Patients With Ataxia Due to Spinocerebellar Degeneration.","authors":"Jin Whan Cho, Jee-Young Lee, Han-Joon Kim, Joong-Seok Kim, Kun-Woo Park, Seong-Min Choi, Chul Hyoung Lyoo, Seong-Beom Koh","doi":"10.14802/jmd.24127","DOIUrl":"10.14802/jmd.24127","url":null,"abstract":"<p><strong>Objective: </strong>We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD).</p><p><strong>Methods: </strong>Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks.</p><p><strong>Results: </strong>A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower \"Stance\" and \"Speech disturbance\" subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05).</p><p><strong>Conclusion: </strong>Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":" ","pages":"35-44"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}