Biomarkers for Therapy of FSHD (U54)

一个多中心团队提议建立一个Wellstone合作研究中心，专注于识别生物标志物，以评估面部肩胛肱肌营养不良症（FSHD）的临床试验结果。在项目1中，Dr. K. Wagner （Johns Hopkins medical Sen）将领导一项关于Acceleron的I期临床试验，以评估其肌肉生长抑制素抑制剂ACE-031对健康人类受试者的影响，为评估其在FSHD中的应用做准备。在项目2中，dr。L.M. Kunkel（哈佛医学院），M. Zatz（圣保罗大学）和R.J. Bloch（马里兰大学医学院）将使用活检样本来鉴定FSHD中rna和蛋白质的变化，目的是鉴定其他疾病生物标志物，并了解它们在肌肉生长抑制素阻断后如何在健康人体肌肉中发生变化。项目3，由博士领导。C.P. Emerson Jr.（波士顿生物医学研究所：bri）和W. Wright（德克萨斯大学西南医学中心）将从FSHD和正常活检中获得原代和不朽的肌源细胞系，以确定生物标志物并检查其在肌肉细胞增殖、分化和发病机制中的作用。项目4由J.B. Miller博士（BBRI）与Bloch博士合作领导，将使用小鼠模型和培养的人类细胞来分析FSHD生物标志物并确定疾病机制。细胞和组织核心（Core C）将与合作医生一起收集和整理FSHD患者和健康志愿者的肌肉活检。该中心还将成为维护和分发该中心开发的FSHD和正常肌原细胞系的国际资源。由Emerson博士领导的行政核心（核心A）将组织项目科学家之间的定期会议，并将与D. Perez先生（FSH协会）合作进行社区外展，并组织一次关于FSHD的年度公开科学会议。核心A将与由Bloch博士领导的教育和培训核心（核心B）协调这项活动，后者每年将支持两名学员，并将组织一年一度的中心静修活动。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研究人员提供新试剂，评估肌肉生长抑制素抑制剂作为潜在的FSHD治疗药物，并为培养年轻科学家构建一个优秀的环境。与公共卫生相关。Wellstone中心将确定FSHD的生物标志物，用于评估临床试验的结果。

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.