Nephrotic Syndrome Rare Disease Clinical Research Network III

摘要 局灶性和节段性肾小球硬化(FSGS)、微小病变(MCD)和膜性 肾病(MN)，表现为肾病综合征(NS)，是一种罕见的疾病，可造成灾难性的后果 并发症和终末期肾病，造成巨大的个人、社会和经济负担。 以临床和组织病理学为基础的NS分类学是不充分的，并且未能捕捉到 这些疾病并不能充分预测其自然病史或对治疗的反应。精确度 医学(PM)方法对于从分子方面定义NS、确定治疗靶点和 将病人与治疗方法配对。海王星被应用了一种创新的调查战略，以改善 肾病综合征的诊断、处理和治疗。在前两个项目期间，翻译和临床 研究基础设施已建立，参与者已登记，生物样本已收集，关键合作 制定并部署了外展战略。海王星已经建立了一个强大的调查基础设施 包括26个学术中心和两个患者兴趣小组，已经严格招募了750多人 具有详细的临床、组织学、遗传学、转录组和蛋白质组数据集的表型NS参与者。 这一综合信息已被整合到海王星知识网络中，以便 NS研究社区。在患者利益集团NephCure Kidney的大力支持下 在国际上，海王星已经建立了强有力的培训和辅助学习计划，有112个辅助计划 研究范围从方法开发到成功的第二阶段临床试验。这些关键的进步有 导致对NS临床试验产生了浓厚的兴趣，目前有15项以上的试验处于高级计划或 注册阶段。 在此续订申请中，我们建议利用海王星资源来催化发现、培训 我们努力改善受非典型肺炎影响的个人的健康状况。首要目标是 将PM方法应用于NS，利用在 过去的9年里。海王星将实施这一PM战略，以允许发现新的治疗靶点和 部署当前资助周期中开发的患者分层方法，以帮助确定正确的试验 在正确的时间选择正确的患者：将使用患者分层方法进行有针对性的登记 临床试验。患者将在出现疾病或随访肾脏时进行密集的侧写。 活组织检查，以使疾病机制与正在进行的竞争前的公共临床试验相匹配 与该领域的领先公司建立私人伙伴关系。培训、试点和辅助研究方案将 继续从NKI获得大量资金支持。海王星将继续与Lay合作 社区、临床医生、科学家、监管机构和制药行业识别和迁移 通过针对NS的有效转译研究渠道，为我们的患者提供治疗目标。

ABSTRACT Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN), presenting as Nephrotic Syndrome (NS), are rare diseases causing catastrophic complications and end stage kidney disease, generating enormous individual, societal and economic burdens. The clinical, histopathology-based taxonomy of NS is inadequate and fails to capture the molecular bases of these diseases and does not adequately predict their natural history or response to therapy. A Precision Medicine (PM) approach is necessary to define NS in molecular terms, to identify therapeutic targets and match patients to treatments. NEPTUNE was applied an innovative, investigational strategy to improve the diagnosis, management and treatment of NS. In the first two project periods, a translational and clinical research infrastructure has been established, participants enrolled, biosamples collected, key collaborations forged and an outreach strategy deployed. NEPTUNE has established a robust investigative infrastructure encompassing 26 academic centers and two patient interest groups, has recruited more than 750 rigorously phenotyped NS participants with detailed clinical, histological, genetic, transcriptomic and proteomic data sets. This comprehensive information has been integrated in the NEPTUNE Knowledge Network for easy access by the NS research community. With substantial support from the patient interest group NephCure Kidney International, NEPTUNE has established robust training and ancillary study programs with 112 ancillary studies ranging from methods development to successful Phase II clinical trials. These critical advances have resulted in a significant interest in NS clinical trials, with more than 15 trials now in the advanced planning or enrollment phase. In this renewal application, we propose to leverage the NEPTUNE resources to catalyze discovery, training and outreach as we strive to improve health outcomes for individuals affected by NS. The overarching goal is to apply a PM approach to NS, leveraging the extensive NEPTUNE Knowledge Network established over the past 9 years. NEPTUNE will implement this PM strategy to permit discovery of novel therapeutic targets and deploy the patient stratification approach developed in the current funding cycle to help identify the right trial for the right patient at the right time: Patient stratification approaches will be utilized for targeted enrollment into clinical trials. Patients will undergo intense profiling at the time of disease presentation or at follow-up renal biopsy in order to match the disease mechanism active with ongoing clinical trials in a precompetitive, public private partnership with leading companies in the field. Training, pilot and ancillary study programs will continue with significant funding support from NKI. NEPTUNE will maintain its engagement with lay communities, clinicians, scientists, regulatory agencies and the pharmaceutical industry to identify and move therapeutic targets to our patients through an effective translational research pipeline for NS.