Optimizing Phenogenotypic and Neuromodulation Predictors in Deep BrainStimulation Surgery for Isolated Dystonia

优化单纯性肌张力障碍深部脑刺激手术中的表型和神经调节预测因子

• 批准号: 10225398
• 负责人: Marta San Luciano
• 金额: $ 20万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225398
• 关键词: Address; Affect; Award; Brain; Cephalic; Characteristics; Clinical; Clinical Research; Clinical Trials; Code; DNA Binding; DNA Binding Domain; DYT1 gene; DYT6 gene; Data; Data Set; Decision Making; Deep Brain Stimulation; Deformity; Devices; Disease; Dystonia; Etiology; Foundations; Frequencies; Future; GAG Gene; Gene Mutation; Genes; Genetic; Genetic Predisposition to Disease; Genetic Transcription; Genotype; Goals; Heterogeneity; Human Genetics; Image; Individual; International; Knowledge; Lead; Life; Limb structure; Location; Medical Genetics; Mentors; Methodology; Motor; Movement; Movement Disorders; Mutation; Nature; Neuroepidemiology; Operative Surgical Procedures; Orthopedics; Outcome; Pacemakers; Parkinson Disease; Patients; Penetrance; Persons; Pharmacotherapy; Phase; Phenotype; Physiology; Population; Posture; Procedures; Proteins; Rare Diseases; Reporting; Research; Research Project Grants; Resources; Spasm; Syndrome; TOR1A gene; Training; Translational Research; Treatment outcome; Variant; Work; brain surgery; career; curative treatments; data repository; design; disability; epidemiology study; experience; illness length; implantation; improved outcome; individual response; negative affect; neuroregulation; personalized medicine; personalized therapeutic; precision medicine; programs; reduce symptoms; responders and non-responders; response; side effect; skills; surgery outcome; symptom treatment

PROJECT SUMMARY/ABSTRACT Dystonia is a hyperkinetic movement disorder characterized by repetitive pulling movements and abnormal postures. Primary (isolated) dystonia is the third most common movement disorder, is often progressive and disabling. Adequate therapies for this illness are needed as there is not yet a cure. The available drug treatments are only symptomatic in nature, frequently associated with incomplete symptom relief and significant side effects. Deep brain stimulation (DBS) surgery can be a life altering symptomatic treatment for some persons with dystonia, but in others there is little benefit. The determinants of a good response to DBS are not known. Poor benefit following DBS may be due to heterogeneity in the genetic etiology and variability in the clinical presentation of dystonia. This project will address these knowledge gaps, focusing on identifying those factors associated with satisfactory clinical outcomes in dystonia. I will take advantage of a unique population to investigate these questions: the data repository of the Bachmann-Strauss Dystonia and Parkinson Foundation (BSDPF) Centers of Excellence Consortium, a repository of data on DBS dystonia patients from four U.S. centers, with the common goal of sharing clinical, genetic, motor physiology and imaging data. This dataset includes our well-characterized DBS treated dystonia population at UCSF, one of the largest populations of surgically-treated people with dystonia world wide. This project focuses on understanding how genetic causes and phenotype of dystonia predict motoric benefit. In the larger coalition population, all DBS cases from four experienced DBS centers will be screened for known mutations and genetic modifiers, and longitudinal surgical motor and disability rating scales will be compared among different mutations and phenotypes with the goal of determination of specific characteristics associated with greatest improvement. The results from this study will allow us to understand important factors that underline responsiveness to DBS, information that is critical to designing the most effective personalized treatments in dystonia. This proposed research project fits nicely with my long-term career goal of becoming a neuroepidemiology expert in developing personalized therapeutics for dystonia and other movement disorders. My training plan in this award includes course work and extensive mentored tutorials to further develop my epidemiological research skills and clinical trial methodology, and increase my knowledge of DBS mechanisms and human genetics. The knowledge and training acquired from this award will allow me to emerge as a leader in this evolving field of individualized precision medicine and address relevant unmet needs in dystonia.

项目总结/文摘

项目成果

Washout of chronic therapeutic deep brain stimulation increases cortical phase-amplitude coupling.

慢性治疗性深部脑刺激的清除会增加皮质相位-幅度耦合。

• DOI: 10.1016/j.parkreldis.2019.08.018
• 发表时间: 2019
• 期刊: Parkinsonism & related disorders
• 影响因子: 4.1
• 作者: Rajagopalan,SheilaS;Miller,AndrewM;deHemptinne,Coralie;SanLuciano,Marta;Ostrem,JillL;Starr,PhilipA
• 通讯作者: Starr,PhilipA

Benign paroxysmal torticollis: phenotype, natural history, and quality of life.

• DOI: 10.1038/s41390-020-01309-1
• 发表时间: 2021-11
• 期刊: Pediatric research
• 影响因子: 3.6
• 作者: Greene KA;Lu V;Luciano MS;Qubty W;Irwin SL;Grimes B;Gelfand AA
• 通讯作者: Gelfand AA

Nonsteroidal Anti-inflammatory Use and LRRK2 Parkinson's Disease Penetrance.

• DOI: 10.1002/mds.28189
• 发表时间: 2020-10
• 期刊: Movement disorders : official journal of the Movement Disorder Society
• 作者: San Luciano M;Tanner CM;Meng C;Marras C;Goldman SM;Lang AE;Tolosa E;Schüle B;Langston JW;Brice A;Corvol JC;Goldwurm S;Klein C;Brockman S;Berg D;Brockmann K;Ferreira JJ;Tazir M;Mellick GD;Sue CM;Hasegawa K;Tan EK;Bressman S;Saunders-Pullman R;Michael J. Fox Foundation LRRK2 Cohort Consortium
• 通讯作者: Michael J. Fox Foundation LRRK2 Cohort Consortium

Phenomenology and Management of Subthalamic Stimulation-Induced Dyskinesia in Patients With Isolated Dystonia.

孤立性肌张力障碍患者底丘脑刺激诱发的运动障碍的现象学和治疗。

• DOI: 10.1002/mdc3.12946
• 发表时间: 2020
• 期刊: Movement disorders clinical practice
• 影响因子: 4
• 作者: Bledsoe,IanO;Dodenhoff,KristenA;SanLuciano,Marta;Volz,MonicaM;Starr,PhilipA;Markun,LeslieC;Ostrem,JillL
• 通讯作者: Ostrem,JillL