Biomarkers for Therapy of FSHD (U54)

描述(由申请人提供)：一个多中心团队建议建立一个韦尔斯通合作研究中心，专注于识别生物标记物，以评估面肩肩周肌营养不良(FSHD)临床试验的结果。在项目1中，K.Wagner博士(Johns Hopkins Med Sen)将领导Acceleron的I期临床试验，以评估其肌肉生长抑素抑制剂ACE-031对健康受试者的影响，为评估其在FSHD中的使用做准备。在项目2中，L.M.昆克尔博士(哈佛医学院)、M.Zatz博士(U Sao Paolo)和R.J.Bloch博士(加州大学马里兰医学院)将使用活检样本来确定FSHD中RNA和蛋白质的变化，目的是确定其他疾病生物标志物，并了解在肌肉抑制素阻断后，这些生物标志物如何在健康的人类肌肉中发生变化。项目3，由小C.P.艾默生博士领导。波士顿生物医学研究所(BBRI)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永生肌源性细胞系，以确定生物标志物并研究它们在肌肉细胞增殖、分化和发病中的作用。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生物标记物并确定疾病机制。细胞和组织核心(核心C)将与合作的医生合作，收集和管理来自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配FSHD和中心培养的正常肌源性细胞系的国际资源。由艾默生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)合作开展社区宣传，并组织关于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)协调这一活动，该核心将支持每年两名受训人员，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确定和测试用于开发新疗法的FSHD生物标记物，为世界各地的FSHD研究人员提供新的试剂，评估肌肉生长抑制素抑制剂作为潜在的FSHD治疗药物，并构建一个培养年轻科学家的杰出环境。与公共卫生的相关性。拟议的韦尔斯通中心将确定FSHD的生物标记物，可用于评估临床试验的结果。

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.