SUPRASPINAL TARGETS IN NEUROGENIC VOIDING DYSFUNCTION

神经源性排尿功能障碍的脊髓上靶点

• 批准号: 9766278
• 负责人: Rose Khavari
• 金额: $ 15.68万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-17 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766278
• 关键词: Address; Anisotropy; Area; Ataxia; Bladder; Bladder Control; Bladder Dysfunction; Brain; Brain region; Catheterization; Catheters; Clinical; Clinical Trials; Clinical trial protocol document; Data; Data Analyses; Databases; Department chair; Development; Development Plans; Diagnostic Procedure; Diffuse; Diffusion Magnetic Resonance Imaging; Etiology; Exhibits; Experimental Designs; Faculty; Failure; Feasibility Studies; Female; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Hand; Hematuria; Human; Individual; Infection; International; Journals; K-Series Research Career Programs; Kidney; Kidney Failure; Lower Extremity; Lower urinary tract; Magnetic Resonance Imaging; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Multiple Sclerosis; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Neurogenic Bladder; Neuropathy; Neurosciences; Outcome Study; Pain; Patients; Pattern; Peer Review; Phase; Program Development; Protocols documentation; Quality of life; Questionnaires; Relaxation; Research; Research Personnel; Research Support; Role; SECTM1 gene; Scientist; Seminal; Sepsis; Signal Transduction; Spasm; Sphincter; Stroke; Surgeon; Syndrome; Therapeutic; Time; Trauma; Urethra; Urinary Retention; Urinary tract infection; Urodynamics; Urology; Work; blood oxygen level dependent; career development; cohort; cost; design; dexterity; gray matter; high risk; improved; interest; meetings; mind control; multidisciplinary; multiple sclerosis patient; nervous system disorder; neuroimaging; neuroregulation; novel diagnostics; novel therapeutics; patient oriented research; pilot trial; predicting response; side effect; therapy development; urologic; white matter

Project Summary/Abstract Dr. Khavari is in her final year of the Multidisciplinary K12 Urologic Research Career Development Program (Lamb: Director; Boone: Co-Director) from NIDDK and is applying for the Individual Career Development Award (K23) to support her transition into a fully independent surgeon-scientist in the fields of neurourology and voiding dysfunction. K23 award will specifically provide Dr. Khavari the support needed to develop expertise in 2 areas: (1) Advanced functional Magnetic Resonance Imaging (fMRI) protocol design and data analysis; (2) Application of Transcranial Rotating Permanent Magnet Stimulator (TRPMS) in a clinical trial. To achieve her goals, Dr. Khavari has assembled an expert multidisciplinary team of collaborators and advisors in neuroimaging (Karmonik), neuroscience (Masdeu and Helekar), neurourology (Chai and Daneshgari), and urologic research (Boone and Lamb). Dr. Boone, the chair of her Department, is a leading expert in neuro-urological research and has mentored many junior faculty to independent investigators and will serve as her Primary Mentor. Neurogenic voiding dysfunction (VD) is morbid, costly, and leads to urinary tract infections, stones, sepsis, and permanent renal failure. Currently, the only available therapy for VD is catheterization, which is a burden, especially in neurogenic patients, such as Multiple Sclerosis (MS), who commonly exhibit lower extremity spasms and compromised hand dexterity. The cost and morbid side effects (hematuria, pain, trauma, strictures, and infections) associated with catheterizations, urge us to look into potential therapeutic options beyond the bladder, such as supraspinal targets. Yet, the current understanding of supraspinal centers, and their roles in initiating or modulating voiding, is rudimentary in patients with neurogenic VD. Dr. Khavari will use preliminary data and the raw database from her established simultaneous fMRI and urodynamics platform to determine whether, in female MS subjects: Aim 1: Activation patterns of preselected grey matter Regions of Interest (ROI)s are different among MS patients with versus without VD, specifically those with Detrusor Sphincter Dyssenergia. Aim 2: Damage to preselected white matter tracts involved in bladder control provides an independent predictive measure for VD. Aim 3: Targeted cortical stimulation in ROIs in MS patients with VD causes changes in ROIs that better recapitulate the activation patterns in patients without VD or healthy controls. Aim 3 will be a pilot trial using an individualized TRPMS targeting personalized ROIs in selected MS patients with VD. Dr. Khavari’s ongoing research and current career development plans exemplify her commitment to becoming an independent investigator in patient-oriented research. Her project has the potential to improve our ability to understand brain control of bladder, suggest new diagnostic methods, and provide crucial steps towards therapeutic options for the morbid and intractable condition, VD, in patients with neurogenic (e.g. MS or Strokes) or non-neurogenic VD (e.g. underactive bladder or Fowler’s syndrome). This proposal, and the subsequent planed R01, will lay the foundation for future clinical trials addressing therapies for VD.

项目摘要/摘要 Khavari博士是多学科K12泌尿外科研究职业发展计划的最后一年 (Lamb：董事；Boone：联席董事)来自NIDDK，正在申请个人职业发展奖 (K23)支持她在神经病学和排尿学领域转变为一名完全独立的外科医生和科学家 功能障碍。K23奖项将专门为Khavari博士提供在两个领域发展专业知识所需的支持： (1)先进功能磁共振成像(FMRI)方案设计与数据分析；(2)应用 经颅旋转式永磁刺激器(TRPMS)的临床试验。为了实现她的目标，Dr。 Khavari组建了一支由神经成像领域的合作者和顾问组成的多学科专家团队 (Karmonik)、神经科学(Masdeu和Helekar)、神经病学(Chai和Daneshgari)和泌尿学研究 (布恩和兰姆)。布恩博士是她所在系的主任，是神经神经学研究和 曾指导许多初级教员成为独立调查人员，并将担任她的主要导师。 神经源性排尿功能障碍(VD)是一种病态的、代价高昂的疾病，并会导致尿路感染、结石、败血症和 永久性肾功能衰竭。目前，唯一可用的治疗方法是导尿术，这是一种负担， 尤其是神经源性患者，如多发性硬化症(MS)，他们通常表现为下肢 痉挛和手部灵巧性受损。成本和病态副作用(血尿、疼痛、创伤、狭窄、 和感染)，促使我们研究潜在的治疗方案 膀胱，如脊柱上靶点。然而，目前对棘上中枢的理解，以及它们 在神经源性VD患者中，启动或调节排尿的作用是基本的。哈瓦里博士将 使用她建立的同步功能磁共振成像和尿动力学平台的初步数据和原始数据库 确定在女性多发性硬化症受试者中：目标1：预选灰质区域的激活模式 伴和不伴VD的MS患者的兴趣区S不同，尤其是有逼尿肌的患者 括约肌神经功能障碍。目标2：对参与膀胱控制的预选白质束的损害提供 一种独立的预测VD的指标。目的3：靶向皮质刺激治疗多发性硬化症患者的感兴趣区 导致感兴趣区的变化，更好地概括了无VD患者或健康对照组的激活模式。 AIM 3将是一项试点试验，在选定的MS患者中使用针对个性化ROI的个性化TRPMS 患有痴呆症。哈瓦里博士正在进行的研究和目前的职业发展计划体现了她对 成为以患者为中心的研究的独立调查者。她的项目有可能改善我们的 能够理解大脑对膀胱的控制，提出新的诊断方法，并提供关键步骤 神经源性疾病(如多发性硬化症或多发性硬化症)患者的病态和难治性疾病的治疗选择 中风)或非神经源性血管性痴呆(如膀胱活动不足或福勒综合征)。这项建议，以及 随后计划的R01，将为未来针对VD治疗的临床试验奠定基础。