Brain Vascular Malformation Consortium: Predictors of clinical course.

一个多学科、跨机构的研究小组，长期对脑血管感兴趣 畸形公司建议建立一个RDCRC。研究中的疾病是常见的西班牙裔突变 家族性海绵状血管畸形(CCM)、斯特奇-韦伯综合征(SWS)和脑动静脉畸形 遗传性出血性毛细血管扩张症的畸形(BAVM)。这三个项目将集中在(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，工作 与RDCRN DMCC合作；(B)开发具有近期潜力的疾病进展标志 用于辅助预测和临床试验发展。CCM的目标包括对基因的鉴定 使用全基因组的横断面和纵向研究设计中疾病进展的标志物 联想方法。SWS的目的是利用尿液中血管生成介质的排泄作为标志物 对于疾病的发展。此外，我们将建立体细胞突变作为潜在的疾病机制。 着眼于将这些知识转变为生物标记物战略。HHT的目标包括 横断面和纵向研究中对颅内出血风险的定量评估 设计，利用血管构筑特征和炎症基因的遗传变异。试点项目 将评估针对这些疾病的新治疗策略，包括在SWS和 出血性血管畸形的四环素类药物。我们将在加州大学旧金山分校使用CTSA或GCRC， 杜克大学、新墨西哥州大学、肯尼迪·克里格大学和加州大学。多伦多，有一个详细的培训新员工的计划 罕见病临床研究的研究人员。三个国际患者支持组织 (PSO)血管瘤联盟、斯特奇·韦伯基金会、国际HHT基金会将积极 参与进来。与DMCC合作，我们将开发一个网站，作为网上数据输入的门户，并包括 为患者、家属和专业人士提供广泛的信息。我们将利用已建立的网络 SWS和HHT中的卓越中心，以识别患者。这个RDCRC将提供一个急需的和 为临床神经血管界研究这三种疾病提供了宝贵的资源。

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.