Biomarkers for Therapy of FSHD (U54)

FSHD 治疗的生物标志物 (U54)

• 批准号: 7932575
• 负责人: CHARLES P. EMERSON
• 金额: $ 34.28万
• 依托单位: BOSTON BIOMEDICAL RESEARCH INSTITUTE
• 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 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932575
• 关键词: Biomarkers; Therapy; FSHD; U54

DESCRIPTION (provided by applicant): A multi-center team proposes to establish a Wellstone Cooperating Research Center focused on identifying biomarkers to evaluate outcomes of clinical trials for facioscapulohumeral muscular dystrophy (FSHD). In Project 1, Dr. K. Wagner (Johns Hopkins Med Sen) will lead a Phase I clinical trial with Acceleron to assess the effects of its myostatin inhibitor, ACE-031, on healthy human subjects, preparatory to assessing its use in FSHD. In Project 2, Drs. L.M. Kunkel (Harvard Med Sch), M. Zatz (U Sao Paolo), and R.J. Bloch (U Maryland Sch Med) will use biopsy samples to identify changes in RNAs and proteins in FSHD, with the aims of identifying additional disease biomarkers and learning how they are altered in healthy human muscle upon myostatin blockade. Project 3, led by Drs. C.P. Emerson Jr. (Boston Biomedical Research Institute: BBRI) and W. Wright (U Texas Southwestern Medical Center), will derive primary and immortal myogenic cell lines from FSHD and normal biopsies to identify biomarkers and examine their role in proliferation, differentiation, and pathogenesis of muscle cells. Project 4, led by Dr. J.B. Miller (BBRI) in collaboration with Dr. Bloch, will use mouse models and cultured human cells to analyze FSHD biomarkers and identify disease mechanisms. The Cell and Tissue Core (Core C) will work with collaborating physicians to collect and curate muscle biopsies from FSHD patients and healthy volunteers. The Core will also be an international resource to maintain and distribute FSHD and normal myogenic cell lines developed in the Center. An Administrative Core (Core A) led by Dr. Emerson will organize regular meetings among the project scientists and will work with Mr. D. Perez (The FSH Society) for community outreach and to organize an annual open scientific meeting on FSHD. Core A will coordinate this activity with the Education and Training Core (Core B), led by Dr. Bloch, which will support two trainees/yr and will organize an annual Center retreat. The Center's research, core, and training activities are thus aimed at identifying and testing FSHD biomarkers for development of new therapies, providing novel reagents for FSHD researchers worldwide, assessing myostatin inhibitors as a potential FSHD therapeutic, and structuring an outstanding environment for training young scientists. Relevance to Public Health. The proposed Wellstone Center will identify biomarkers for FSHD that can be used for evaluating outcomes in clinical trials.

描述（由申请人提供）：一个多中心团队提议建立一个井石合作研究中心，重点是识别生物标志物，以评估Facioscapulohumeral肌肉营养不良（FSHD）的临床试验结果。在项目1中，K。Wagner博士（Johns Hopkins Med Sen）将与Acceleron进行I期临床试验，以评估其肌生抑制剂抑制剂ACE-031对健康人类受试者的影响，以评估其在FSHD中的使用。在项目2中，博士。 L.M. Kunkel（Harvard Med Sch），M。Zatz（U Sao Paolo）和R.J. Bloch（U Maryland Sch Med）将使用活检样本来识别FSHD中RNA和蛋白质的变化，以鉴定其他疾病生物标志物并学习如何在肌抑制素阻断后健康的人类肌肉中改变它们。项目3，由博士领导。 C.P. Emerson Jr.（波士顿生物医学研究所：BBRI）和W. Wright（U Texas Southwestern Medical Center）将从FSHD和正常活检中得出原发性和不朽的成肌细胞系，以识别生物标志物并检查其在肌肉细胞的增殖，分化，分化和致病性中的作用。由J.B. Miller博士（BBRI）领导的项目4与Bloch博士合作，将使用小鼠模型和培养的人类细胞来分析FSHD生物标志物并识别疾病机制。细胞和组织核心（核心C）将与合作医生合作，从FSHD患者和健康志愿者那里收集和策划肌肉活检。核心也将是一种国际资源，用于维护和分发中心开发的FSHD和正常的肌源细胞系。由艾默生（Emerson）博士领导的行政核心（核心A）将在项目科学家中组织定期会议，并将与D. Perez（FSH协会）合作进行社区宣传，并组织一次FSHD的年度公开科学会议。核心A将与Bloch博士领导的教育和培训核心（Core B）协调这项活动，该活动将支持两名受训者/年，并将组织年度中心务虚会。因此，该中心的研究，核心和培训活动旨在识别和测试FSHD生物标志物以开发新疗法，为全球FSHD研究人员提供新颖的试剂，评估肌汀抑制剂作为潜在的FSHD治疗疗法，并为培训年轻科学家的杰出环境构建了杰出的环境。与公共卫生有关。拟议的Wellstone中心将识别FSHD的生物标志物，可用于评估临床试验中的结果。