Brain Vascular Malformation Consortium: Predictors of clinical course

描述(申请人提供)：脑血管畸形联合会(BVMC)专注于三种相对罕见的血管畸形：脑海绵状畸形(CCM)、斯特奇-韦伯综合征(SWS)和遗传性出血性毛细血管扩张症(HHT)。每一种疾病的生物学机制都知之甚少，需要大量资源才能有效地进行管理，并且极有可能出现严重的神经系统疾病，如出血、癫痫发作和局灶性神经功能缺陷。所有这三种疾病都有一个共同的生物学主题：基于血管形成或维持的正常生理机制失败的脑血管表型。最近的数据还表明，这三种疾病在分子信号通路上有共同之处。每种疾病都具有广泛的表型特征，对其生物学风险因素知之甚少。这些危险因素的识别将对患者监测和优化管理具有直接意义。此外，尽管目前还没有针对这些疾病的特定药物疗法，但适当的治疗试验将需要生物标记物来对患者的选择和替代结果进行风险分层。在我们最初的项目期间，我们为所有三种疾病建立了信息丰富的患者登记，并在识别MRI方面取得了重大进展， 与特定临床结果相关的遗传和生化生物标记物。基于这一坚实的基础，我们现在建议BVMC的更新集中于三个具体目标：1)继续为HHT、SWS和CCM开发强大的患者登记；2)继续识别和验证HHT、SWS和CCM的临床相关生物标志物；以及3)帮助开展HHT、SWS和CCM的未来临床研究。这些目标将通过我们的三个项目、CORE、试点项目和培训部分以及与患者倡导团体--血管瘤联盟、斯特奇·韦伯基金会、国际HHT基金会--以及RDCRN数据管理和协调中心的积极合作来实现。BVMC的建立是促进跨疾病合作的重要一步，为研究提供了一个集中的临床研究基础设施 这三种罕见的疾病，并为更大的神经血管社区产生了宝贵的资源。

DESCRIPTION (provided by applicant): The Brain Vascular Malformation Consortium (BVMC) focuses on three relatively rare vascular malformations: Cerebral Cavernous Malformation (CCM), Sturge-Weber Syndrome (SWS), and Hereditary Hemorrhagic Telangiectasia (HHT). Each is poorly understood in terms of biological mechanisms, resource intensive to manage effectively, and has high probability of serious neurological morbidity, such as hemorrhage, seizures and focal neurological deficits. All three diseases share a common biological theme: a brain vascular phenotype based on failure of the normal physiological mechanisms of blood vessel formation or maintenance. Recent data also suggests that the three diseases share commonalities in their molecular signaling pathways. Each disease is characterized by a wide spectrum of phenotypes, for which biological risk factors are poorly understood. The identification of these risk factors would be of immediate significance for patient surveillance an for optimizing management. Further, although there are no specific medical therapies for these diseases, appropriate treatment trials will require biomarkers to risk stratify patients for selecton and surrogate outcomes. In our original project period, we established information-rich patient registries for all three diseases, and made significant progress towards the identification of MRI, genetic, and biochemical biomarkers associated with specific clinical outcomes. Based on this strong foundation, we now propose the renewal of the BVMC focused on three Specific Aims: 1) To continue to develop robust patient registries for HHT, SWS, and CCM; 2) To continue to identify and validate clinically relevant biomarkers for HHT, SWS, and CCM; and 3) To aid the development of future clinical research studies for HHT, SWS, and CCM. These aims will be accomplished through our three Projects, Cores, pilot project and training components, and active collaborations with the Patient Advocacy Groups - Angioma Alliance, Sturge Weber Foundation, HHT Foundation International - and the RDCRN Data Management and Coordinating Center. Establishment of the BVMC has been a major step forward in promoting cross-disease collaborations, providing a centralized clinical research infrastructure for studying these three rare diseases, and generating a valuable resource for the larger neurovascular community.