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：
9353717
负责人：
KEVIN M FLANIGAN
金额：
$ 148.7万
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/9353717
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 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 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 research clinical testing 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.

总体cort 抽象的全国儿童医院研究所基因治疗中心（RINCH）具有针对肌肉营养不良的专用翻译程序，对开发有意义形式的有意义的疗法的特别长期兴趣，包括Duchenne肌肉营养不良症（DMD）和facioscapulohumeral肌营养不良症（FSHD）。我们中心的目标包括阐明疾病发病机理和发展新的可以从长凳上翻译成床边的治疗范例，然后 Cort建议我们试图加速这一翻译过程。项目1（PI，Paul Martin， PhD）寻求扩展一种疗法，现在以DMD的试验进入其他形式的肌肉营养不良，通过施加galgt2的过表达，galgt2是一种将骨骼肌糖基化改变至的酶增强蛋白质改善疾病的表达。项目2（PI，Scott Harper，博士）探索新颖的方法来调节Dux4基因的表达以治疗相对常见和使人衰弱的FSHD。项目3（PI，Kevin Flanigan，MD）试图快速翻译新发现的肌营养不良蛋白转化为有意义的疗法的机制 DMD男孩。这三个项目都使用两个关键研究核心：治疗病毒向量设计与发展研究核心（PI，Louise Rodino-Klapac，PhD）和肌肉营养不良细胞和血清银行核心（PI，Kim McBride，MD）。除了调查人员在这里由项目代表，拟议的Cort代表更大的肌肉全国儿童和俄亥俄州立大学的疾病研究基础，为此描述了发达的飞行员和可行性计划。这个建议的科特是一致的凭借尼亚姆人的使命，它的目标是为改善患有肌肉疾病形式的患者的生活质量。