Center of Research Translation in Muscular Dystrophy Therapeutic Development

肌营养不良症治疗开发研究翻译中心

基本信息

批准号：
9767664
负责人：
KEVIN M FLANIGAN
金额：
$ 144.31万
依托单位：
RESEARCH INST NATIONWIDE CHILDREN'S HOSP
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-14 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9767664
关键词：
Address Animal Model Basic Science Biological Markers Cells Child Clinic Clinical Clinical Trials Data Development Disease Doctor of Philosophy Duchenne muscular dystrophy Dystrophin Enzymes Exons Facioscapulohumeral Muscular Dystrophy Fibroblasts Funding GDF8 gene Gene Transfer Genes Goals Human Innovative Therapy Internal Ribosome Entry Site Intramuscular Knowledge Limb structure Mission Modeling Molecular Muscle Muscular Dystrophies Mutation Myoblasts Myopathy National Institute of Arthritis and Musculoskeletal and Skin Diseases Ohio Other Genetics Pathogenesis Patients Pediatric Hospitals Polypeptide N-acetylgalactosaminyltransferase Preclinical Testing Principal Investigator Process Production Protein Isoforms Quality of life RNA Interference RNA Splicing Research Research Institute Research Personnel Research Project Grants Resources Ribosomes Sampling Serum Skeletal Muscle Testing Tetanus Helper Peptide Therapeutic Therapeutic Uses Translating Translational Research Translations United States National Institutes of Health Universities Untranslated RNA Viral Vector Work adeno-associated viral vector base bench to bedside boys congenital muscular dystrophy design effective therapy exon skipping experience first-in-human gene therapy glycosylation human disease improved industry partner interest muscle form novel novel strategies novel therapeutics overexpression pre-clinical preclinical development programs protein expression research and development therapeutic development therapy development transcription factor transdifferentiation type 1a limb girdle muscular dystrophy vector

项目摘要

Overall CORT Abstract The Center for Gene Therapy at The Research Institute of Nationwide Children's Hospital (RINCH) has a dedicated translational program that targets the muscular dystrophies, with a particular longstanding interest in developing meaningful therapies for the most common forms, including Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Our Center's goals include unraveling disease pathogenesis and developing new treatment paradigms that can be translated from the bench to the bedside, and under this CORT proposal we seek to accelerate this translational process. Project 1 (PI, Paul Martin, PhD) seeks extend a therapy now entering trials in DMD to other forms of muscular dystrophy, by applying the overexpression of Galgt2, an enzyme that alters skeletal muscle glycosylation to boost the expression of proteins that ameliorate disease. Project 2 (PI, Scott Harper, PhD) explores novel approaches to modulating the expression of the DUX4 gene to treat the relatively common and debilitating FSHD. Project 3 (PI, Kevin Flanigan, MD) seeks to rapidly translate a newly discovered mechanism for dystrophin translational control into meaningful therapy for boys with DMD. All three projects make use of two critical research cores: the Therapeutic Viral Vector Design and Development Research Core (PI, Louise Rodino-Klapac, PhD) and the Muscular Dystrophy Cell and Serum Banking Core (PI, Kim McBride, MD). In addition to the investigators represented here by projects, the proposed CORT represents a larger muscle disease research base at the Nationwide Children's and the Ohio State University, for which a well-developed pilot and feasibility program is described. This proposed CORT is consistent with the mission of NIAMS, which has the goal of finding effective treatments for and to improving the quality of life of patients with debilitating forms of muscle disease.

整体CORT 抽象的全国儿童医院研究所基因治疗中心（RINCH）有一个针对肌营养不良症的专门转化计划，对针对最常见形式开发有意义的疗法有着特别长期的兴趣，包括杜氏肌营养不良症 (DMD) 和面肩肱型肌营养不良症（FSHD）。我们中心的目标包括揭示疾病发病机制和开发新的可以从实验室转移到床边的治疗范例，在此之下我们寻求 CORT 提案来加速这一转化过程。项目 1（PI，保罗·马丁，博士）寻求将目前正在进入 DMD 试验的疗法扩展到其他形式的肌营养不良症，通过应用 Galgt2（一种改变骨骼肌糖基化的酶）的过度表达促进改善疾病的蛋白质的表达。项目 2（PI，Scott Harper，博士）探索调节 DUX4 基因表达的新方法来治疗相对常见且使人衰弱的 FSHD。项目 3（PI，Kevin Flanigan，医学博士）旨在快速转化新发现的抗肌营养不良蛋白翻译控制机制转化为有意义的治疗患有 DMD 的男孩。所有三个项目都利用了两个关键的研究核心：治疗性病毒矢量设计和开发研究核心（PI，Louise Rodino-Klapac 博士）和肌营养不良症细胞和血清库核心（PI，Kim McBride，医学博士）。除了此处由项目代表的研究人员表示，拟议的 CORT 代表了更大的力量全国儿童医院和俄亥俄州立大学的疾病研究基地，描述了完善的试点和可行性计划。这个提议的CORT是一致的 NIAMS 的使命是寻找有效的治疗方法并改善患有使人衰弱的肌肉疾病的患者的生活质量。