NOVEL THERAPY FOR RESISTANT FOCAL SEGMENTAL GLOMERULOSCLEROSIS

抵抗性局灶节段性肾小球硬化症的新疗法

• 批准号: 7608248
• 负责人: HOWARD TRACHTMAN
• 金额: $ 5.07万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608248
• 关键词: Accounting; Adult; Agonist; Antibodies; Childhood; Chronic; Computer Retrieval of Information on Scientific Projects Database; Deterioration; Dialysis procedure; Disease; Drug Kinetics; Etiology; Fibrosis; Focal Segmental Glomerulosclerosis; Funding; Future; Grant; Hybrids; Incidence; Institution; Kidney; Kidney Diseases; Medical; Outcome Study; Patients; Performance; Phase; Phase II Clinical Trials; Phased Innovation Awards; Physical Dialysis; Randomized Clinical Trials; Rate; Research; Research Infrastructure; Research Personnel; Resistance; Resources; Safety; Source; Staging; Testing; Transforming Growth Factors; Transplantation; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States National Institutes of Health; design; human TNF protein; novel; therapeutic target; therapy resistant

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 0099 Primary focal segmental glomerulosclerosis (FSGS) is a serious renal disease, accounting for nearly 10-15% of all pediatric and adult patients requiring chronic dialysis or transplantation. Not only is the incidence of this disease rising. The etiology of FSGS remains obscure and there is no proven therapy. In the absence of a well-defined therapeutic target and a candidate treatment, this proposal will evaluate the safety and efficacy of three novel agents that may have the capacity to reduce renal fibrosis and slow the rate of deterioration of disease in patients with resistant FSGS. The Phased Innovation Award application is composed of two distinct portions. During the initial stage, the R21 Phase, the safety, tolerance, and pharmacokinetic profile of two novel therapies - a TNF-a (tumor necrosis factor-a) antagonist and a PPARg agonist -- will be tested. In the second stage, the R33 phase, a hybrid ranking and selection Phase II study will be performed to assess the efficacy of these two treatments and an anti-TGF-b (tumor growth factor-b)antibody compared to optimal conservative medical therapy. The outcome of this study will guide the design of a formal Phase III randomized clinical trial. The infrastructure that is established for the performance of this R21/R33 project should prove useful for the efficient assessment of additional novel therapies that will to arise in the future.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 0099 原发性局灶性节段性肾小球硬化症（FSGS）是一种严重的肾脏疾病，占所有需要慢性透析或移植的儿科患者和成年患者的近10-15％。这种疾病的发生率不仅上升。 FSG的病因仍然晦涩难懂，没有经过验证的疗法。在没有明确定义的治疗靶点和候选治疗的情况下，该提案将评估三种新型药物的安全性和功效，这些新药物可能具有降低肾纤维化的能力并减慢耐药性FSG患者的疾病恶化率。分阶段创新奖的应用程序由两个不同的部分组成。在初始阶段，将测试两种新型疗法的R21阶段，安全性，耐受性和药代动力学特征 - TNF-A（肿瘤坏死因子-A）拮抗剂和PPARG激动剂。在第二阶段，将进行R33阶段，即与最佳保守医疗疗法相比，将进行一项混合排名和选择阶段II研究，以评估这两种治疗方法和抗TGF-B（肿瘤生长因子-B）抗体的功效。这项研究的结果将指导正式的III期随机临床试验的设计。为该R21/R33项目的性能而建立的基础设施应被证明是对未来将要出现的其他新型疗法的有效评估有用的。