Brain Vascular Malformation Consortium: Predictor's of Clinical Course

脑血管畸形联盟：临床过程的预测因子

• 批准号: 9804270
• 负责人: Helen Kim
• 金额: $ 175.99万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9804270
• 关键词: Affect; Biochemical; Biological; Biological Markers; Blood Vessels; Brain; Brain Vascular Malformation; Brain imaging; Caring; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Data; Databases; Development; Disease; Disease Progression; Drug Monitoring; Enrollment; Ensure; FDA approved; Faculty; Failure; Focal Neurologic Deficits; Foundations; Funding; GNAQ gene; Generations; Genetic; Genotype; Goals; Hemangioma; Hemorrhage; Hemorrhagic Disorders; Hereditary hemorrhagic telangiectasia; Heterogeneity; Inflammatory; Investigation; Knowledge; Lesion; Magnetic Resonance Imaging; Maintenance; Measurable; Medical; Medical Genetics; Molecular; Morbidity - disease rate; Mutation; National Institute of Neurological Disorders and Stroke; Nature; Neurologic; Outcome; Paper; Patients; Pharmaceutical Preparations; Phenotype; Physiological; Pilot Projects; Probability; Protein Biochemistry; Publishing; Quality of life; Rare Diseases; Readiness; Research; Research Infrastructure; Research Personnel; Resources; Risk; Risk stratification; Sampling; Seizures; Seminal; Signal Pathway; Signal Transduction; Specimen; Students; Sturge-Weber Syndrome; Symptoms; Therapeutic Clinical Trial; Therapeutic Trials; Training; Training Programs; Vascular Diseases; Work; base; biobank; biomarker identification; blood vessel development; brain arteriovenous malformations; burden of illness; career development; cerebral cavernous malformations; clinical development; clinical predictors; clinical research site; cost; cost effective; data management; design; efficacy study; follow-up; functional outcomes; high risk; improved; insight; neurovascular; next generation; novel; novel therapeutics; patient advocacy group; patient registry; response; therapeutic candidate

Abstract The Brain Vascular Malformation Consortium (BVMC) focuses on three rare vascular diseases with brain involvement: Cerebral Cavernous Malformation (CCM), Sturge-Weber Syndrome (SWS), and Hereditary Hemorrhagic Telangiectasia (HHT). Each is poorly understood in terms of biological mechanisms leading to progression to clinical symptoms, are resource-intensive to manage effectively, and has high probability of serious neurological morbidity. All three share a common biological theme: a brain vascular phenotype based on failure of the normal physiological mechanisms of blood vessel formation or maintenance. There is considerable overlap in the nature of the neurological morbidity of these disorders: hemorrhage, seizures and focal neurological deficits are common causes of poor functional outcome and significantly affect patient quality of life. Recent advances have also identified several dysregulated cell-signaling pathways in common, which has treatment implications. Over the past 5 years, rapid basic and translational advances have identified several candidate therapeutics, many of which are already FDA-approved for other indications and could be repurposed for use in CCM, SWS or HHT. However, much work is still needed to prepare for pending drug trials in patients with these rare diseases. In the next cycle, our projects propose to focus on clinical trial readiness issues to help inform trials, by identifying and validating biologically relevant biomarkers that can be used for monitoring drug response and identifying measurable outcomes for trial development. The overall goal of the BVMC is to facilitate and advance high-quality clinical research in CCM, SWS, and HHT by providing research infrastructure and maintaining longitudinal patient registries and biorepositories (Aim 1), by identifying and validating clinical outcomes and biomarkers for use in clinical trials (Aim 2), and by training the next generation of rare disease researchers and funding high-risk/high-payoff pilot studies (Aim 3). These aims will be accomplished through our three Projects, Cores, pilot project and training components; active collaborations with the Patient Advocacy Groups – Angioma Alliance, Sturge Weber Foundation, Cure HHT; 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.

摘要 脑血管畸形联盟（BVMC）专注于三种罕见的脑血管疾病， 累及：脑海绵状血管畸形（CCM）、Sturge-Weber综合征（SWS）和遗传性 出血性毛细血管扩张症（HHT）。每一个都是知之甚少的生物机制，导致 进展为临床症状，需要大量资源才能有效管理， 严重的神经系统疾病。所有这三种都有一个共同的生物学主题： 血管形成或维持的正常生理机制的失败。有 这些疾病的神经系统发病率的性质有相当大的重叠：出血、癫痫发作 和局灶性神经功能缺损是功能结局不良的常见原因， 生活质量最近的进展还确定了几个失调的细胞信号通路， 常见的，这有治疗意义。 在过去的5年里，快速的基础和转化进展已经确定了几种候选疗法， 其中许多已被FDA批准用于其他适应症，并可重新用于CCM、SWS 或HHT。然而，仍然需要做很多工作来准备这些罕见的患者的未决药物试验。 疾病在下一个周期，我们的项目建议重点关注临床试验准备问题，以帮助通知试验， 通过鉴定和验证可用于监测药物反应的生物学相关生物标志物， 确定试验开发的可测量结果。BVMC的总体目标是促进和推动 通过提供研究基础设施和维护高质量的CCM，SWS和HHT临床研究 纵向患者登记和生物储存库（目标1），通过识别和验证临床结局， 用于临床试验的生物标志物（目标2），并通过培训下一代罕见疾病研究人员， 资助高风险/高回报的试点研究（目标3）。这些目标将通过我们的三个项目来实现， 核心、试点项目和培训组成部分;与患者倡导团体积极合作-血管瘤 联盟、Sturge Weber基金会、Cure HHT和RDCRN数据管理和协调中心。 BVMC的建立是促进跨疾病合作的重要一步， 一个集中的临床研究基础设施，用于研究这三种罕见疾病，并产生有价值的 更大的神经血管社区的资源。