Muscular Dystrophy Specialized Research Center

肌营养不良症专业研究中心

• 批准号: 10652506
• 负责人: KEVIN P. CAMPBELL
• 金额: $ 146.65万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-08 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10652506
• 关键词: Acceleration; Advisory Committees; Basic Science; Binding; Biochemical; Biological Markers; Biopsy; Blood; Cell Culture Techniques; Cells; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Communication; Communities; Community Outreach; Cryopreservation; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Dystroglycan; Environment; Fellowship; Fibroblasts; Functional disorder; Genes; Genotype; Goals; Human Resources; Infrastructure; Iowa; Laboratories; Laminin; Length; Measures; Medical Students; Mission; Molecular; Motor; Muscle; Muscle function; Muscular Dystrophies; Myoblasts; Myocardial tissue; Natural History; Neuromuscular Diseases; Patient Care; Patients; Pediatric Neurology; Postdoctoral Fellow; Property; Proteins; Proteomics; Qualifying; Regulation; Research; Research Personnel; Resource Sharing; Resources; Role; Scientist; Severities; Skeletal Muscle; Structure; Testing; Tissues; Training; Translating; Translational Research; Translations; United States National Institutes of Health; Universities; Urine; alpha Dystroglycan; cell repository; clinical care; clinical research site; clinical translation; clinical trial readiness; cohort; dystroglycanopathy; follow-up; fukutin related protein; graduate school; improved; insight; interest; medical schools; member; mouse model; muscle degeneration; next generation; novel; novel diagnostics; novel therapeutic intervention; patient engagement; pre-clinical; programs; rational design; receptor function; recruit; repository; skills; sugar; tissue culture; tissue/cell culture; training opportunity; undergraduate research; undergraduate student; user-friendly; web site

OVERALL SUMMARY The overall goal of the University of Iowa Wellstone Muscular Dystrophy Specialized Research Center (MDSRC) is to perform research on the various muscular dystrophies that arise from abnormal processing of the dystroglycan protein (dystroglycanopathies). The Center will achieve this overall goal by conducting basic and translational research in dystroglycanopathy patients, patient-derived biosamples, and mouse models. Our MDSRC application is composed of two projects and three cores, all of which are directed by investigators with a proven track record of excellence and collaboration in basic, translational and clinical research. Project 1 (Campbell) will investigate the cellular and molecular mechanisms that underly dystroglycanopathies by evaluating the relationship between α-dystroglycan (α-DG) matriglycan length and its laminin-binding properties in control and dystroglycanopathy patient fibroblasts and muscle biopsies. Additional studies will define the requirements for matriglycan synthesis as regulated by protein-protein and protein-sugar interactions. A dystroglycanopathy mouse model will be utilized to identify novel pathophysiologic mechanisms and determine the structure and laminin binding properties required to improve muscle function. Project 2 (Mathews) will refine the natural history of FKRP-related dystroglycanopathy derived from an established, unique cohort of patients by expanding the number of clinical sites evaluating patients and by extending the natural history study to patients with more advanced clinical severity. Extended follow up of non-FKRP genotypes will identify cohorts that share similar rates of motor progression who might be studied together in gene non-specific clinical trials. Candidate proteomic biomarkers in blood or urine for the full spectrum of dystroglycanopathy genotypes will be validated and related to disease status. Core A (Campbell and Moore) is an administrative core that will coordinate the activities within and outside the Center, as a means to promote an interactive and collaborative research environment, and to engage patients in muscular dystrophy research. Core B (Moore), a Muscle-Tissue/Cell-Culture/Diagnostics Core, will support Projects 1 and 2, serve as a national tissue and cell-culture resource for research, provide specialized diagnostic testing for a wide range of muscular dystrophies, and maintain the infrastructure needed to evaluate muscle biopsies in support of clinical trials. Finally, Core C (Mathews and Campbell) will coordinate our Training initiatives. Among the support this Core provides will be fellowships enabling two medical students per year to perform research in the Center and to participate in the care of patients alongside Dr. Mathews, with basic science training opportunities also provided to a postdoctoral fellow and an undergraduate research fellow. The highly integrated cores and projects of this Center will accelerate the tempo of discovery in preclinical translational research, and also establish the clinical-trial readiness of a cohort of dystroglycanopathy patients.

整体总结

项目成果

Large1 gene transfer in older myd mice with severe muscular dystrophy restores muscle function and greatly improves survival.

• DOI: 10.1126/sciadv.abn0379
• 发表时间: 2022-05-27
• 期刊: Science advances
• 影响因子: 13.6

Structural basis of laminin binding to the LARGE glycans on dystroglycan.

• DOI: 10.1038/nchembio.2146
• 发表时间: 2016-10
• 期刊: Nature chemical biology
• 影响因子: 14.8
• 作者: Briggs DC;Yoshida-Moriguchi T;Zheng T;Venzke D;Anderson ME;Strazzulli A;Moracci M;Yu L;Hohenester E;Campbell KP
• 通讯作者: Campbell KP

Development and Validation of a Western Blot Method to Quantify Mini-Dystrophin in Human Skeletal Muscle Biopsies.

• DOI: 10.1208/s12248-022-00776-0
• 发表时间: 2022-12-20
• 期刊: The AAPS journal

Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy.

• DOI: 10.1038/s41434-021-00300-7
• 发表时间: 2022-11
• 期刊: GENE THERAPY
• 影响因子: 5.1
• 作者: Farrokhi, Vahid;Walsh, Jason;Palandra, Joe;Brodfuehrer, Joanne;Caiazzo, Teresa;Owens, Jane;Binks, Michael;Neelakantan, Srividya;Yong, Florence;Dua, Pinky;Le Guiner, Caroline;Neubert, Hendrik
• 通讯作者: Neubert, Hendrik

Cell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function.

• DOI: 10.1038/s41467-022-31205-7
• 发表时间: 2022-06-24
• 期刊: Nature communications
• 影响因子: 16.6