Movement Disorders最新文献

{"title":"Beyond the Homunculus-SCAN-AMN as a Shared Action-Oriented Neural Substrate across Movement Disorders.","authors":"Arjun Balachandar,Alvaro Hernandez-Guillen,Nico U F Dosenbach,Anthony E Lang,Christos Ganos","doi":"10.1002/mds.70259","DOIUrl":"https://doi.org/10.1002/mds.70259","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"1 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Open-Label Phase 1b Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of ANX005 in Patients with Huntington's Disease.","authors":"Rajeev Kumar,Pinky Agarwal,Karen Anderson,Daniel Claassen,Marissa Dean,Andrew Duker,Burton Scott,Benjamin Hoehn,Ann Mongan,Ping Lin,Ellen Cahir-McFarland,Lori Taylor,Glenn Morrison,Ted Yednock,Sanjay Keswani,Henk-Andre Kroon","doi":"10.1002/mds.70229","DOIUrl":"https://doi.org/10.1002/mds.70229","url":null,"abstract":"BACKGROUNDThe classical complement pathway is implicated in the progression of neurodegenerative disease through its ability to drive aberrant removal of synapses, neuroinflammation, and neuronal damage. ANX005 is a humanized monoclonal antibody targeting C1q that blocks classical complement pathway activation.OBJECTIVEThe aim was to assess the safety, pharmacokinetics (PK), pharmacodynamics, and clinical activity of ANX005 in patients with Huntington's disease (HD).METHODSANX005-HD-01 (NCT04514367) was a multicenter, open-label, phase 1b study in patients with early-manifest HD. Primary endpoints included safety, tolerability, PK, and complement C1q and C4a/C4 levels in the serum and cerebrospinal fluid (CSF). Exploratory clinical activity endpoints included changes from baseline in composite Unified Huntington's Disease Rating Scale (cUHDRS) and component scores.RESULTSAll patients who received study drug (n = 28) experienced ≥1 treatment-emergent adverse event, mostly transient infusion-related reactions on the first dose. Three patients with elevated baseline antinuclear antibodies withdrew from the study due to treatment-related AEs (pneumonitis) or serious AEs (systemic lupus erythematous, hemolysis). Twenty-three patients (82.1%) received all planned ANX005 infusions. Steady-state PK was achieved by week 6, with full saturation of ANX005 observed in serum and the CSF. Stabilization or possible improvement in cUHDRS and total functional capacity through 36 weeks was observed in a patient subgroup with higher baseline complement activity, based on baseline C4a/C4 ratio in CSF.CONCLUSIONOverall, AEs with ANX005 administration were manageable, and most patients received all planned doses. Evidence of clinical improvement with ANX005 was observed in patients with higher baseline complement activity, supporting future study in patients with HD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"122 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When the Scale Drops: Pathways to Weight Loss in Parkinson's Disease and Future Directions.","authors":"Ellie D Gabriel,Robert S Eisinger,Joyce M Lee,Sarah Hamimi,Hope Kim,Susanna D Howard,Casey H Halpern","doi":"10.1002/mds.70258","DOIUrl":"https://doi.org/10.1002/mds.70258","url":null,"abstract":"Although Parkinson's disease (PD) is classically defined by its motor features, non-motor symptoms exert a substantial and often under-recognized influence on disease trajectory. Among these, weight loss has long been observed in PD and other neurodegenerative disorders, yet the mechanisms remain incompletely understood. This limited mechanistic insight has left few treatment options for weight loss in PD. Emerging research highlights the role of metabolic regulation, neuroendocrine signaling, pharmacologic treatment, cognitive decline, gastrointestinal dysfunction, and brain stimulation in shaping weight trajectories in PD. In this review, we synthesize current evidence surrounding weight in PD, beginning with an overview of epidemiologic trends and their implications for morbidity and mortality. The sections that follow examine proposed mechanisms, clinical and treatment-related factors associated with weight change, and insights derived from deep brain stimulation studies. Finally, we summarize cross-mechanism interactions, current knowledge gaps and discuss practical recommendations for translating these insights into therapeutic strategies. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"245 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advertising to Healthcare Professionals: Insights from Parkinson's Disease in the Movement Disorders Journal","authors":"Augusto Rachão MD, António Silva MD, Luísa Prada MD, Joana Pona-Ferreira MD, Margherita Fabbri MD, PhD, Filipe B. Rodrigues MD, Tiago A. Mestre MD, PhD, Miguel Coelho MD, PhD, Mário M. Rosa MD, PhD, Werner Poewe MD, Olivier Rascol MD, PhD, Francisco E.C. Cardoso MD, PhD, Joaquim J. Ferreira MD, PhD","doi":"10.1002/mds.70108","DOIUrl":"10.1002/mds.70108","url":null,"abstract":"<p>The pharmaceutical industry promotes the prescription of drugs and medical devices through multiple strategies. While direct-to-consumer (DTC) advertising is banned in most countries worldwide because of concerns about misleading information, advertising directed at healthcare professionals – especially in medical journals – remains legal, widespread, and profitable.<span><sup>1-5</sup></span> This raises important questions about the influence of promotional strategies on clinical decision-making.</p><p>A key distinction in advertising lies between propositional and non-propositional content. Advertising texts, images, photographs, or other graphic elements are considered propositional if they make explicit claims about a product that can be judged as true or false (eg, statements about efficacy). Non-propositional content, in contrast, cannot be evaluated as true or false but nevertheless shapes attitudes and behavior.<span><sup>3, 6</sup></span> For example, a journal advertisement might depict a patient happily engaging in an outdoor activity, implicitly suggesting recovery from any symptoms they previously had, or use imagery (such as a plateau) to symbolize a drug mechanism of action (namely an extended-release formulation).</p><p>Such techniques often work subconsciously, bypassing critical judgment and appealing to emotion rather than evidence. In this way, they may influence physicians' beliefs and behaviors, regardless of the explicit claims being made.<span><sup>3, 6</sup></span> Still, despite their relevance, they remain largely underexplored and analyzed in medical advertising.</p><p>Parkinson's disease (PD) can offer a particularly valuable case study to examine trends in medical advertising to healthcare professionals over the years. Since the introduction of levodopa in the 1960s, the PD market has expanded considerably to include a wide range of drugs and devices (Fig. 1). Surprisingly, little has been published on how these products are advertised to physicians; only one prior study, which ended in 1980, has addressed this topic.<span><sup>7</sup></span></p><p>To shed light on how marketing strategies for PD have evolved over time, and what this evolution reveals about the relationship between persuasion, evidence, and clinical practice, we reviewed and catalogued PD-related advertisements for drugs and devices that were published over nearly four decades (1986–2024) in the highly-ranked subspecialty journal, <i>Movement Disorders</i>.</p><p>In total, we identified 109 unique PD advertisements, covering 30 therapeutic products. Two distinct phases of advertising emerged (Fig. 2). Before 2008, advertisements were dominated by PD drugs, frequently relying on non-propositional elements. While no PD advertisements were identified between 2009 and 2012, from 2013 onwards, drug advertisements declined, while those for deep brain stimulation (DBS) devices increased, becoming the dominant form of PD advertising in this Journal.</p><","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 2","pages":"337-341"},"PeriodicalIF":7.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Movement Disorders: Volume 41, Number 2, February 2026","authors":"","doi":"10.1002/mds.70240","DOIUrl":"10.1002/mds.70240","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 2","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Evaluation of an Abbreviated Patient-Reported Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) for Predicting Dopaminergic Therapy Initiation in Early Parkinson's Disease","authors":"Mohammad Samsul Alam PhD,&nbsp;Luowen Yu MS,&nbsp;Glenn T. Stebbins PhD,&nbsp;Tiago A. Mestre MD, PhD,&nbsp;Christopher G. Goetz MD,&nbsp;Sheng Luo PhD","doi":"10.1002/mds.70096","DOIUrl":"10.1002/mds.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Predicting initiation of dopaminergic therapy in early Parkinson's disease (PD) is important for clinical management and trial design. Prior cross-sectional work identified a six-item patient-reported subset from the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts IB + II, but its longitudinal utility is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To test whether modeling longitudinal symptom trajectories improves prediction of dopaminergic therapy initiation beyond baseline-only models, and to identify an abbreviated patient-reported subset with stable prognostic value and utility for trial stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were harmonized from 1787 untreated early PD patients across six multicenter studies. All 20 MDS-UPDRS Parts IB + II items were analyzed using a longitudinal item response theory model. Items were ranked by discrimination and information functions, and cumulative subsets evaluated in Cox models with time-dependent covariates, adjusted for age, sex, disease duration, and Hoehn and Yahr stage. Predictive accuracy was quantified by concordance index (C-index) for full follow-up and truncation at 1 and 2 years. Risk stratification was assessed based on baseline abbreviated subset scores using Kaplan–Meier analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An 11-item model consistently outperformed the full 20-item scale (C-index 0.609 vs. 0.597, <i>P</i> &lt; 0.001 with full follow-up; 0.621 vs. 0.599, <i>P</i> &lt; 0.001 at 1 year; 0.615 vs. 0.602, <i>P</i> &lt; 0.001 at 2 years). Longitudinal updates improved discrimination over baseline-only models (eg, 0.609 vs. 0.594 for full follow-up). Higher baseline 11-item scores were strongly associated with earlier therapy initiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Longitudinal symptom modeling improves prediction of therapy initiation in early PD. An abbreviated 11-item patient-reported MDS-UPDRS provides stronger prognostic value than the full scale and supports trial stratification and clinical monitoring. © 2025 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 2","pages":"426-435"},"PeriodicalIF":7.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145374084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Multi-Omics Analysis Prioritizes Candidate Genes for Essential Tremor and Reveals a Gap Between Computational Prediction and Experimental Validation","authors":"Aishanjiang Yusufujiang MD,&nbsp;Shan Zeng MD,&nbsp;Likun Xu,&nbsp;Gong Li,&nbsp;Zebin Wang,&nbsp;Hongyan Li MD, PhD","doi":"10.1002/mds.70101","DOIUrl":"10.1002/mds.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The genetic architecture of essential tremor (ET) remains incompletely understood. A key challenge is translating genome-wide association study (GWAS) loci into specific effector genes to elucidate disease mechanisms and develop targeted therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To implement a multistage computational framework to prioritize high-confidence candidate genes for ET and to assess these predictions against publicly available, patient-derived transcriptomic data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed a convergent evidence strategy to prioritize genes, integrating cross-tissue (UTMOST) and tissue-specific (FUSION) transcriptome-wide association studies (TWAS) with gene-based association tests (MAGMA). Prioritized genes were subjected to causal inference analyses (summary-data-based Mendelian randomization [SMR] and colocalization), co-expression network analysis (GeneMANIA), and pharmacogenomic analysis (DGIdb). We leveraged spatial transcriptomics to characterize gene expression patterns across cortical layers and cell types. Finally, we validated computational predictions using two independent post-mortem brain datasets from ET patients and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our prioritization pipeline identified 12 high-confidence candidate genes. Co-expression network analysis revealed 83.3% of candidates exhibit functional relationships, forming three modules centered on RNA processing (<i>NRBP1</i>), metabolic regulation (<i>SLC5A6</i>), and nucleotide synthesis (<i>CAD</i>). Pharmacogenomic analysis demonstrated 66.7% of candidates possess therapeutic target potential. Spatial transcriptomics revealed preferential expression in cortical Layer 5 pyramidal neurons. However, validation in post-mortem cerebellar tissue showed no significant differential expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study provides a robust pipeline for ET gene prioritization and puts forward a novel cortical hypothesis for the disease. The discordance between strong computational predictions and their lack of validation in available patient tissue highlights a critical gap in the field. © 2025 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 2","pages":"351-360"},"PeriodicalIF":7.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Brain Calcification: An International Consensus on Nomenclature, Diagnosis, Evaluation, and Management","authors":"Wei Luo MD, PhD,&nbsp;Zhidong Cen MD, PhD,&nbsp;Huiberdina Koek MD,&nbsp;Miryam Carecchio MD, PhD,&nbsp;Isao Hozumi MD, PhD,&nbsp;Wan-Jin Chen MD, PhD,&nbsp;Amit Batla MD, FRCP,&nbsp;Alexander Balck MD,&nbsp;Francesca Magrinelli MD, PhD,&nbsp;Dehao Yang MD, PhD,&nbsp;Xuewen Cheng PhD,&nbsp;Ana Westenberger PhD,&nbsp;Akiyoshi Kakita MD, PhD,&nbsp;Liam Chen MD, PhD,&nbsp;Christian Lambert PhD,&nbsp;Jing-Yu Liu PhD,&nbsp;Annika Keller PhD,&nbsp;João Ricardo Mendes de Oliveira MD,&nbsp;Zhi-Qi Xiong PhD,&nbsp;Henry Houlden MD, PhD,&nbsp;Kailash P. Bhatia MD, FRCP,&nbsp;Christine Klein MD,&nbsp;Gaël Nicolas MD, PhD","doi":"10.1002/mds.70140","DOIUrl":"10.1002/mds.70140","url":null,"abstract":"<p>Our understanding of primary brain calcification (PBC) has accelerated with the identification of seven causative genes over the past 13 years, vastly expanding knowledge of the molecular underpinnings of this disorder. Despite this progress, a lack of standardized clinical definitions, variable presentations, and heterogeneous calcification patterns has perpetuated inconsistencies in diagnosis and patient care. To address these challenges, an international expert panel undertook a comprehensive process—combining systematic literature review, virtual and in-person expert discussions, and iterative Delphi consensus questionnaires—to develop unified recommendations. These consensus guidelines encompass terminology, diagnostic criteria, neuroimaging protocols, clinical evaluation standards, genetic testing approaches, and management strategies. Notably, PBC is recommended as the clinical standard, with new diagnostic criteria, including the use of a computed tomography–based total calcification score and a three-tiered diagnostic algorithm (possible, probable, definite PBC). A systematic review of 27 symptoms and signs identified 19 as most closely linked with PBC, guiding more focused clinical assessment. Recommendations strongly support comprehensive next-generation sequencing for genetic testing, favoring whole genome over exome or targeted panels to maximize diagnostic yield. Multidisciplinary management priorities are outlined in four key principles centering on individualized care, symptom relief, genetic counseling, and ongoing monitoring. Widespread adoption of these unified guidelines will facilitate consistent diagnosis, enable comparative international data collection, and lay the groundwork for large-scale collaborative research—including future randomized controlled trials of symptomatic and disease-modifying PBC therapies. This consensus fosters clarity and consistency, creating a framework for improved patient care and scientific discovery. © 2025 International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 2","pages":"315-336"},"PeriodicalIF":7.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain–Computer Interface Improves Symptoms of Isolated Focal Laryngeal Dystonia: A Single-Blind Study","authors":"Stefan K. Ehrlich PhD,&nbsp;Garrett Tougas BS,&nbsp;Jacob Bernstein BA,&nbsp;Nicole Buie BS,&nbsp;Anna F. Rumbach PhD,&nbsp;Kristina Simonyan MD, PhD, Dr Med","doi":"10.1002/mds.70114","DOIUrl":"10.1002/mds.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and objective</h3>\u0000 \u0000 <p>Laryngeal dystonia (LD) is a focal task-specific dystonia, affecting speaking but not whispering or emotional vocalizations. Therapeutic options for LD are limited. We developed and tested a non-invasive, closed-loop, neurofeedback, brain–computer interface (BCI) intervention for LD treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ten patients with isolated focal LD participated in the study. The personalized BCI system included visual neurofeedback of individual real-time electroencephalographic (EEG) activity during symptomatic speaking compared to asymptomatic whispering, presented in the virtual reality (VR) environment of real-life scenarios. During five consecutive days of intervention, patients used the BCI to learn to modulate their abnormally increased brain activity during speaking and match it to near-normal activity of asymptomatic whispering. Changes in voice symptoms and EEG activity were quantified for the evaluation of BCI effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to baseline, LD patients had a statistically significant reduction of their voice symptoms on Days 1–5 of BCI intervention. Thi was paralleled by improved controllability of the visual neurofeedback and a significant reduction of left frontal delta power, including superior and middle frontal gyri, on Day 1 and left central gamma power, including premotor, primary sensorimotor, and inferior parietal areas, on Days 3 and 5. The majority of patients (70%) reported sustained positive effects of the BCI intervention on their voice quality 1 week after the study participation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The closed-loop BCI neurofeedback intervention specifically targeting disorder pathophysiology shows significant potential as a novel treatment option for patients with LD and likely other forms of task-specific focal dystonia. © 2025 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 2","pages":"406-415"},"PeriodicalIF":7.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRRK2 as a Potential Disease-Modifying Target in Sporadic Parkinson's Disease","authors":"Anthony E. Lang MD,&nbsp;Robert A. Hauser MD,&nbsp;Lorraine V. Kalia MD, PhD,&nbsp;Bonnie Hersh MD,&nbsp;Zdenek Berger PhD,&nbsp;Roy Llorens Arenas MD,&nbsp;Coro Paisan-Ruiz PhD,&nbsp;Kyle Fraser PhD,&nbsp;Danna Jennings MD,&nbsp;Jillian H. Kluss PhD,&nbsp;Sarah Huntwork-Rodriguez PhD,&nbsp;Anastasia G. Henry PhD,&nbsp;J. Timothy Greenamyre MD, PhD","doi":"10.1002/mds.70100","DOIUrl":"10.1002/mds.70100","url":null,"abstract":"<p>A growing understanding of the role that leucine-rich repeat kinase 2 (LRRK2) plays in Parkinson's disease (PD) supports continued focus on this enzyme as a therapeutic target for PD. Accumulating evidence suggests that there are phenotypic, neuropathologic, and biological similarities between sporadic PD (sPD) and familial forms in which <i>LRRK2</i> variants are inherited in an autosomal-dominant pattern with variable penetrance (LRRK2-PD). Further, genome-wide association studies have found specific non-coding variants that are risk factors for sPD. In this review, we describe the current state of knowledge as it relates to LRRK2's role in sPD, with a focus on comparing the physiology and pathology of sPD with LRRK2-PD. As in LRRK2-PD, LRRK2 activity may also be increased in sPD, possibly through interactions between genetics and the environment. Increased activity of LRRK2 and associated endolysosomal dysfunction have been observed in sPD patients, including evidence from postmortem brains of patients with sPD and animal models showing increased LRRK2 activity. Additionally, beneficial effects of LRRK2 inhibitors, such as improved lysosomal function, reduced α-synuclein accumulation, and amelioration of neurodegeneration, have been demonstrated in animal models of sPD. Therefore, inhibition of LRRK2 kinase activity may be a promising approach to disease modification for sPD and LRRK2-PD. Ongoing and future clinical studies examining LRRK2 kinase inhibitors will aim to elucidate their clinical efficacy in PD and to assess their potential effects on lysosomal function. © 2025 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 2","pages":"297-314"},"PeriodicalIF":7.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}