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，以评估面肩肱型肌营养不良症（FSHD）临床试验的结果。在项目1中，K.瓦格纳（约翰霍普金斯医学森）将领导一个I期临床试验与加速，以评估其肌肉生长抑制素抑制剂，ACE-031，对健康的人类受试者的影响，准备评估其在FSHD的使用。在项目2中，L.M.博士Kunkel（哈佛医学院），M. Zatz（U Sao Paolo）和R.J. Bloch（U马里兰州Sch Med）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，并了解肌肉生长抑制素阻断后它们在健康人体肌肉中的变化。项目3，由C.P. Emerson Jr.博士领导。（波士顿生物医学研究所：BBRI）和W. Wright（U Texas Southwestern Medical Center）将从FSHD和正常活检中获得原代和永生肌细胞系，以鉴定生物标志物并研究其在肌细胞增殖，分化和发病机制中的作用。项目4，由J. B.博士领导。米勒（BBRI）与布洛赫博士合作，将使用小鼠模型和培养的人类细胞来分析FSHD生物标志物并确定疾病机制。细胞和组织核心（核心C）将与合作医生合作，收集和策划FSHD患者和健康志愿者的肌肉活检。该核心也将是一个国际资源，以维持和分发FSHD和正常肌细胞系开发的中心。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。佩雷斯（FSH协会）的社区外展，并组织一个年度公开科学会议FSHD。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，后者将每年支助两名受训人员，并将组织中心的年度务虚会。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研究人员提供新试剂，评估肌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出色的环境。与公共卫生相关。拟议的Wellstone中心将确定FSHD的生物标志物，可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.