Brain Vascular Malformation Consortium: Predictors of clinical course.

一个多学科、跨机构的研究小组，长期关注脑血管疾病， 建议设立一个康复中心。研究的疾病是常见的西班牙裔突变 家族性海绵状血管畸形（CCM）、Sturge-Weber综合征（SWS）和脑动静脉畸形 遗传性出血性毛细血管扩张症（HHT）的畸形（BAVM）。这三个项目将侧重于（a） 建立可扩展的关系数据库，以促进观察性研究和临床试验， 和（B）开发具有近期潜力的疾病进展标志物 用于辅助实验和临床试验开发。CCM的目标包括识别遗传 使用全基因组研究设计的横断面和纵向研究设计中的疾病进展标志物 协会的做法。SWS的目的是使用尿排泄的血管生成介质作为标记物 for disease疾病progression进展.此外，我们将建立体细胞突变作为潜在的疾病机制 着眼于将这些知识应用于生物标志物策略。HHT的目标包括 横断面和纵向研究中颅内出血（ICH）风险的定量估计 设计，利用血管结构特征和炎症基因的遗传变异。试点项目 将评估疾病的新治疗策略，包括在SWS中使用阿司匹林， 四环素类药物治疗出血性血管畸形。我们将利用加州大学旧金山分校的CTSA或GCRC， 杜克，新墨西哥州，肯尼迪克里格和大学多伦多，与培训新的详细计划， 罕见病的临床研究。三个国际患者支持组织 （PSO）血管瘤联盟，Sturge Weber基金会，HHT国际基金会将积极 参加我们会与数码城市管理协调中心合作，建立一个网站，作为输入网上数据的入门网站，并会在网站上 为患者、家属和专业人士提供广泛的信息。我们将利用现有的网络， SWS和HHT的卓越中心用于识别患者。该RDCRC将提供急需的和 这是临床神经血管社区研究这三种疾病的宝贵资源。

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.