Brain Vascular Malformation Consortium: Predictors of clinical course

脑血管畸形联盟：临床病程的预测因子

• 批准号: 8113515
• 负责人: WILLIAM L YOUNG
• 金额: $ 6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8113515
• 关键词: Arteriovenous malformation; Aspirin; Biological Markers; Blood Vessels; Brain; Brain Vascular Malformation; Cavernous Malformation; Clinical; Clinical Research; Clinical Trials; Communities; Data; Development; Disease; Disease Progression; Excretory function; Eye; Family; Foundations; Genes; Genetic Markers; Genetic Variation; Hemangioma; Hispanics; Inflammatory; Inherited; International; Intracranial Hemorrhages; Knowledge; Longitudinal Studies; Mediator of activation protein; Medical; Morbidity - disease rate; Mutation; Neurologic; New Mexico; Observational Study; Online Systems; Outcome; Patients; Pilot Projects; Probability; Rare Diseases; Research Design; Research Personnel; Resources; Risk; Somatic Mutation; Stratification; Sturge-Weber Syndrome; Tetracyclines; Training Programs; Work; genome wide association study; improved; interest; malformation; multidisciplinary; novel; progression marker; relational database; treatment strategy; treatment trial; urinary; web site

A multidisciplinary, inter-institutional group of investigators with long-standing interest in brain vascular malformations proposes to establish a RDCRC. The diseases of study are common Hispanic mutation familial Cavernous Malformations (CCM), Sturge-Weber Syndrome (SWS) and Brain Arteriovenous Malformation (BAVM) in Hereditary Hemorrhagic Telangectasia (HHT). The three projects will focus on (a) establishment of scalable, relational databases to facilitate observational studies and clinical trials, working with the RDCRN DMCC; and (b) development of markers for disease progression with near-term potential for aiding prognostication and clinical trial development. The aims for CCM include identification of genetic markers for disease progression in cross-sectional and longitudinal study designs using a Genome-Wide Association approach. The aims for SWS are to use urinary excretion of angiogenic mediators as markers for disease progression. Further, we will establish somatic mutations as an underlying disease mechanism with an eye towards adapting such knowledge into a biomarker strategy. The aims for HHT include quantitative estimation of intracranial hemorrhage (ICH) risk in cross-sectional and longitudinal study designs, using both angioarchitectural features and genetic variation in inflammatory genes. Pilot projects will evaluate novel treatment strategies for the diseases, including the use of aspirin in SWS and tetracycline-class agents in hemorrhagic vascular malformations. We will utilize CTSAs or GCRCs at UCSF, Duke, New Mexico, Kennedy Krieger and Univ. Toronto, with a detailed program for training new investigators in clinical research on rare diseases. Three international Patient Support Organizations (PSOs)-Angioma Alliance, Sturge Weber Foundation, HHT Foundation International-will actively participate. With the DMCC, we will develop a website as a portal for web-based data entry and include a wide range of information for patients, families and professionals. We will utilize a network of established Centers of Excellence in SWS and HHT to identify patients. This RDCRC will provide a much-needed and valuable resource for the clinical neurovascular community for the study of these three disorders.

对脑血管畸形的长期兴趣的多学科，机构间的研究人员建议建立RDCRC。研究的疾病是常见的西班牙裔突变家族性海绵状畸形（CCM），Sturge-Weber综合征（SWS）和遗传性出血性毛道症（HHT）中的脑静脉畸形（BAVM）（HHT）。这三个项目将着重于（a）建立可扩展的关系数据库，以促进与RDCRN DMCC合作的观察性研究和临床试验； （b）开发疾病进展的标志物，其近期潜力有助于预后和临床试验发展。 CCM的目的包括使用全基因组关联方法鉴定横断面和纵向研究设计中疾病进展的遗传标记。 SWS的目的是将血管生成介质的尿排泄作为疾病进展的标志。此外，我们将建立躯体突变为一种潜在的疾病机制，以注重将这种知识调整为生物标志物策略。 HHT的目的包括使用血管结构特征和炎症基因的遗传变异的跨截面和纵向研究设计中颅内出血（ICH）风险的定量估计。试点项目将评估疾病的新型治疗策略，包括在SWS中使用阿司匹林和四环素类药物在出血性血管畸形中。我们将在UCSF，Duke，New Mexico，Kennedy Krieger和Univ使用CTSA或GCRC。多伦多，有一个详细的计划，用于培训有关稀有疾病临床研究的新研究人员。三个国际患者支持组织（PSOS） - 血管瘤联盟，Sturge Weber Foundation，HHT基金会国际将积极参与。借助DMCC，我们将开发一个网站作为基于Web的数据输入的门户网站，并为患者，家庭和专业人员提供广泛的信息。我们将利用SWS和HHT卓越中心的既定中心网络来识别患者。该RDCRC将为临床神经血管社区提供急需和宝贵的资源，以研究这三种疾病。