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: 7943115
• 负责人: WILLIAM L YOUNG
• 金额: $ 120.42万
• 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/7943115
• 关键词: Brain; Vascular; Malformation; Consortium; Predictors

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.

一个多学科、跨机构的研究小组对脑血管畸形有长期的兴趣，建议建立一个RDCRC。研究的疾病是遗传性出血性毛细血管扩张症（HHT）中常见的西班牙突变家族性海绵状血管瘤（CCM）、斯特奇-韦伯综合征（SWS）和脑动静脉畸形（BAVM）。这三个项目将侧重于(a)与RDCRN DMCC合作，建立可扩展的关系型数据库，以促进观察性研究和临床试验；(b)开发具有近期潜力的疾病进展标志物，以帮助预测和临床试验的发展。CCM的目标包括使用全基因组关联方法在横断面和纵向研究设计中识别疾病进展的遗传标记。SWS的目的是使用尿排泄血管生成介质作为疾病进展的标志物。此外，我们将建立体细胞突变作为潜在的疾病机制，并着眼于将这些知识应用于生物标志物策略。HHT的目的包括在横断面和纵向研究设计中定量估计颅内出血（ICH）的风险，同时使用血管结构特征和炎症基因的遗传变异。试点项目将评估这些疾病的新治疗策略，包括在SWS中使用阿司匹林和在出血性血管畸形中使用四环素类药物。我们将利用加州大学旧金山分校、杜克大学、新墨西哥州、肯尼迪克里格大学和多伦多大学的CTSAs或GCRCs，制定详细的计划，培训罕见病临床研究的新研究人员。三个国际患者支持组织（pso）——血管瘤联盟、斯特格·韦伯基金会、国际HHT基金会将积极参与。通过DMCC，我们将开发一个网站，作为基于网络的数据输入的门户，并为患者，家庭和专业人员提供广泛的信息。我们将利用已建立的SWS和HHT卓越中心网络来识别患者。该RDCRC将为临床神经血管界对这三种疾病的研究提供急需的宝贵资源。