Brain Vascular Malformation Consortium: Predictors of clinical course

一个对脑血管畸形长期感兴趣的多学科、跨机构的研究小组建议建立一个RDCRC。所研究的疾病是遗传性出血性延髓扩张症(HHT)中常见的西班牙裔突变家族性海绵状畸形(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)建立可扩展的关系数据库，以促进观察性研究和临床试验，与RDCRN DMCC合作；(B)开发具有近期潜力的疾病进展标志，以帮助预测和临床试验开发。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的目的是利用尿中血管生成介质的排泄作为疾病进展的标志。此外，我们将建立体细胞突变作为潜在的疾病机制，着眼于将这些知识适应于生物标记物策略。HHT的目标包括在横断面和纵向研究设计中使用血管构筑特征和炎症基因的遗传变异来定量评估颅内出血(ICH)的风险。试点项目将评估疾病的新治疗策略，包括在系统性红斑狼疮中使用阿司匹林，在出血性血管畸形中使用四环素类药物。我们将在加州大学旧金山分校、杜克大学、新墨西哥州大学、肯尼迪·克里格大学和大学使用CTSA或GCR。多伦多，有一个详细的计划，培训新的研究人员在罕见疾病的临床研究。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。我们将与DMCC一起开发一个网站，作为基于Web的数据输入的门户，并为患者、家属和专业人员提供广泛的信息。我们将利用在SWS和HHT中建立的卓越中心网络来识别患者。这一RDCRC将为临床神经血管学界研究这三种疾病提供急需和宝贵的资源。

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.