Nephrotic Syndrome Rare Disease Clinical Research Network III

肾病综合征罕见病临床研究网络III

基本信息

批准号：
10480842
负责人：
Matthias Kretzler
金额：
$ 150.46万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-08 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10480842
关键词：
APOL1 gene Address Adopted Adult Affect Africa South of the Sahara African American African American population Ancillary Study Award Biocompatible Materials Biopsy Budgets Child Childhood China Clinical Clinical Research Clinical Trials Cohort Studies Collaborations Communities Data Data Set Diagnosis Disease Disease remission Drug Industry Economic Burden Education and Outreach End stage renal failure Enrollment Environmental Risk Factor Europe Faculty Focal Segmental Glomerulosclerosis Funding Genetic Genetic Markers Genotype Goals Health Histologic Histology Histopathology India Individual Infrastructure Interest Group International Investigation Kidney Kidney Diseases Knowledge Membranous Glomerulonephritis Mentors Molecular Natural History Nephrology Nephrotic Syndrome Online Systems Outcome Participant Pathway interactions Patient Rights Patients Pediatric cohort Phase Phase II Clinical Trials Phenotype Physicians Pilot Projects Postdoctoral Fellow Privatization Proteinuria Proteomics Protocols documentation Rare Diseases Research Research Infrastructure Research Personnel Resources Scientist Sister Taxonomy Time Training Training Programs Translational Research Variant base causal variant clinical phenotype cohort cost effective data management disease classification empowered follow-up genetic architecture health disparity improved individual patient innovation interest kidney biopsy knowledge of results method development molecular phenotype molecular targeted therapies new therapeutic target outreach patient engagement patient stratification phenotypic data precision medicine programs public-private partnership recruit social factors therapeutic target therapy development transcriptomics treatment response

项目摘要

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.

抽象的局灶性和节段性肾小球硬化症 (FSGS)、微小病变病 (MCD) 和膜性肾小球硬化症肾病（MN），表现为肾病综合征（NS），是一种罕见的疾病，会导致灾难性的后果并发症和终末期肾病，产生巨大的个人、社会和经济负担。基于临床、组织病理学的 NS 分类学不够充分，未能捕捉到 NS 的分子基础这些疾病并不能充分预测其自然史或对治疗的反应。精度医学 (PM) 方法对于用分子术语定义 NS、确定治疗靶点和使患者与治疗相匹配。 NEPTUNE 采用了创新的研究策略来改善 NS 的诊断、管理和治疗。在前两个项目期间，转化和临床研究基础设施已建立，参与者已入组，生物样本已收集，关键合作制定并部署了外展战略。 NEPTUNE 建立了强大的调查基础设施涵盖 26 个学术中心和两个患者兴趣小组，已严格招募了 750 多名通过详细的临床、组织学、遗传、转录组和蛋白质组数据集对 NS 参与者进行表型分析。这些综合信息已集成到 NEPTUNE 知识网络中，以便于访问 NS 研究团体。得到患者利益团体 NephCure Kidney 的大力支持在国际上，NEPTUNE 建立了强大的培训和辅助学习计划，拥有 112 个辅助学习项目研究范围从方法开发到成功的二期临床试验。这些关键进展已经引起了人们对 NS 临床试验的浓厚兴趣，目前有超过 15 项试验处于高级计划或招生阶段。在此更新应用程序中，我们建议利用 NEPTUNE 资源来促进发现、培训我们努力改善受 NS 影响的个人的健康结果。总体目标是将 PM 方法应用于 NS，利用在 NEPTUNE 上建立的广泛的 NEPTUNE 知识网络过去9年。 NEPTUNE 将实施这一 PM 策略，以发现新的治疗靶点并部署在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找到正确的患者：将利用患者分层方法进行有针对性的入组临床试验。患者将在出现疾病时或随访肾病时接受严格的分析活检，以便将活跃的疾病机制与正在进行的竞争前、公开的临床试验相匹配与该领域领先公司的私人合作伙伴关系。培训、试点和辅助研究计划将继续获得 NKI 的大力资助。 NEPTUNE 将保持与外行的接触社区、临床医生、科学家、监管机构和制药行业来识别和移动通过有效的 NS 转化研究管道为我们的患者提供治疗目标。