Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy

肌营养不良症的磁共振成像和生物标志物

基本信息

批准号：
8500999
负责人：
KRISTA H VANDENBORNE
金额：
$ 129.74万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-05 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8500999
关键词：
14 year old Activities of Daily Living Address Adipose tissue Adrenal Cortex Hormones Affect Age Ankle Area Biological Markers Biopsy Cell Therapy Cells Cessation of life Characteristics Clinical Clinical Trials Communities Cross-Sectional Studies Deposition Dermal Development Disease Disease Progression Duchenne muscular dystrophy Dystrophin Effectiveness Evaluation Explosion Fatty acid glycerol esters Feedback Fibroblasts Flexor Florida Future Genomics Genotype Glucocorticoids Goals Health Sciences Imaging technology Infiltration Inflammation Intervention Intramuscular Isometric Exercise Knee Limb-Girdle Muscular Dystrophies Link Lipids Longitudinal Studies Lower Extremity Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manuals Measurement Measures Medical Imaging Monitor Mus Muscle Muscle Fibers Muscle Weakness Muscle function Muscular Dystrophies Mutation Myoblasts Myopathy Neuromuscular Diseases Nonsense Codon Oligonucleotides Oregon Outcome Measure Pathogenesis Patients Pediatric Hospitals Pharmacotherapy Phenotype Philadelphia Physiology Preclinical Drug Evaluation Process Property Quality of life Randomized Controlled Trials Relaxation Research Design Resources Sampling Serum Severity of illness Site Skeletal Muscle Source Spectrum Analysis Staging Steroids Structural Protein Subgroup Techniques Technology Testing Therapeutic Effect Therapeutic Intervention Time Tissue Banking Tissue Banks Tissues Translations Universities Validation Walking Water boys design effective therapy gene therapy clinical trial improved information gathering mouse model muscle strength muscular structure outcome forecast preclinical study premature public health relevance quadriceps muscle repository restoration standard measure standard of care tool treatment strategy

项目摘要

DESCRIPTION (provided by applicant): The overall objective of this proposal is to validate the potential of noninvasive magnetic resonance imaging (MRI) and spectroscopy (MRS) to monitor disease progression and to serve as a surrogate outcome measure for clinical trials in Duchenne muscular dystrophy (DMD). DMD is one of the most devastating genetically linked neuromuscular diseases and is characterized by the absence of dystrophin, resulting in progressive muscle weakness, loss of walking ability and premature death. Despite the poor prognosis for patients with muscular dystrophy, therapeutic interventions have been lacking, and outcome measures for clinical trials have been limited to measures of muscle function and quality of life, serum biomarkers of muscle breakdown and invasive muscle biopsies. Additional quantitative outcome measures that are noninvasive and sensitive to changes in muscle structure and composition are needed to facilitate the rapid translation of promising new interventions from preclinical studies to clinical trials. As such, this proposal targets the development and validation of magnetic resonance as a noninvasive biomarker of disease progression in muscular dystrophy. Using a multi-site research design this study will examine the intramuscular lipid content, muscle damage/inflammation and contractile area in the lower extremity muscles of 100 ambulatory boys with DMD and 50 healthy age matched boys using a combination of MRI and MRS technologies. In order to assess the sensitivity of each MR measure to disease progression, all boys with DMD will be re-evaluated in yearly or 6 month intervals. In addition, we will correlate changes in MR measures with standard measures of disease progression, such as loss in muscle strength and functional ability. Using MRI/MRS we will also examine the effect of initiating corticosteroid treatment on skeletal muscle characteristics and composition. Finally, we will deposit immortalized fibroblasts from carefully characterized DMD boys participating in this study in established tissue repositories. We anticipate that the MR techniques developed and validated in this proposal will be suitable for clinical trials in a wide range of muscular dystrophies and other neuromuscular diseases. In addition, MR characterization may serve as a powerful tool to further advance our understanding of the pathogenesis of muscular dystrophy and help guide the design of future trials.

描述（由申请人提供）：该提案的总体目的是验证非侵入性磁共振成像（MRI）和光谱法（MRS）监测疾病进展的潜力，并作为Duchenne Muscular Dystrophy（DMD）临床试验的替代结果指标。 DMD是最具毁灭性的遗传连接神经肌肉疾病之一，其特征是缺乏肌营养不良蛋白，导致渐进的肌肉无力，步行能力的丧失和过早死亡。尽管对肌肉营养不良患者的预后不良，但缺乏治疗性干预措施，临床试验的结果指标限于肌肉功能和生活质量的测量，肌肉崩溃的血清生物标志物和侵入性肌肉生物的生物标志物。需要进行无创和对肌肉结构变化敏感的其他定量结果指标，以促进从临床前研究到临床试验的有希望的新干预措施的快速转化。因此，该提案以磁共振作为肌肉营养不良中疾病进展的无创生物标志物的发展和验证。使用多站点研究设计，这项研究将检查100名具有DMD的Absulatory Boys的下肢肌肉中肌肉内脂质含量，肌肉损伤/炎症和收缩区域，并使用MRI和MRS Technologies的组合结合使用了50个健康年龄的男孩。为了评估每种MR对疾病进展的敏感性，所有DMD男孩的年度将在每年或6个月间隔重新评估。此外，我们将将MR测量的变化与疾病进展的标准度量相关，例如肌肉力量和功能能力的丧失。使用MRI/MRS，我们还将检查启动皮质类固醇治疗对骨骼肌特征和组成的影响。最后，我们将从精心表征的DMD男孩中沉积永生的成纤维细胞，这些男孩在既定的组织存储库中都参加了这项研究。我们预计该提案中开发和验证的MR技术将适用于广泛的肌肉营养不良和其他神经肌肉疾病的临床试验。此外，MR表征可以作为进一步提高我们对肌肉营养不良发病机理的理解并帮助指导未来试验的设计的强大工具。