Therapy Nanoparticles for Modulation of Inflammation in Neuromuscular Disease

用于调节神经肌肉疾病炎症的治疗纳米颗粒

• 批准号: 7941748
• 负责人: SAMUEL A WICKLINE
• 金额: $ 33.86万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941748
• 关键词: Binding; Biological Markers; Blood Vessels; Cardiac; Cessation of life; Clinical; Clinical Management; Deterioration; Development; Diagnosis; Diagnostic; Disease; Dose; Drug Delivery Systems; Drug Formulations; Early identification; Endothelial Cells; Evaluation; Evolution; Experimental Models; Genes; Genetic Materials; Image; Immunohistochemistry; Inflammation; Inflammatory; Integrins; Laboratories; Methods; Molecular; Mus; Muscular Dystrophies; Myocardium; Myopathy; Nanotechnology; Neuromuscular Diseases; Outcome; Pathway interactions; Patients; Pharmaceutical Preparations; Physiological; Process; Reporting; Signal Transduction; Sirolimus; Site; Skeletal Muscle; Steroid therapy; Steroids; Tertiary Protein Structure; Testing; Therapeutic; Tissues; Toxic effect; Ursidae Family; Vascular Cell Adhesion Molecule-1; analytical tool; base; follow-up; human FRAP1 protein; improved; in vivo; mdx mouse; nanoparticle; nanosystems; novel; novel strategies; performance tests; public health relevance; response; skeletal; stem cell therapy

DESCRIPTION (provided by applicant): Although great promise has been shown for therapy of muscular dystrophy by gene and stem cell therapies, and steroids appear to improve physiological function, the complexity of the total disease process and the rapid progression to death in these patients begs for practical alternative strategies. The purpose of this proposal is to develop and evaluate new approaches to multiplexed therapeutics of muscular dystrophy based on recent progress in our laboratory that may bring targeted nanosystems to bear on diagnosis, therapy, and image-based management of muscular dystrophy. In this translational proposal, all of the required synthetic and analytical tools are at our disposal to conclusively determine if a targeted nanotechnology platform adds value to the management of experimental models of muscular dystrophy, which is a proposition that heretofore has never been tested. The overarching hypothesis of this proposal is that: nanotechnology-based approaches add unique and valuable assets to the diagnostic and therapeutic armamentarium in neuromuscular disorders, and will contribute in a directly translational way to the clinical management of neuromuscular disorders. The deliverables, or outcomes, envisioned in the specific aims and outlined in the experimental plan are: 1) Formulation of nanoparticles targeted to inflammatory biomarkers of disease to noninvasively, sensitively, and accurately report the activity and the evolution of the muscular dystrophy disease process through image- based readouts of selected molecular biomarkers of pathophysiological significance to the early inflammatory changes that contribute to the deterioration of cardiac and skeletal muscle; 2) Development of novel methods for repeated delivery of potent drugs and genetic materials to targeted sites of inflammation with reduced toxicity profiles as compared with current therapeutic approaches; and 3) Integration of image-based readouts of disease activity in conjunction with therapeutic delivery to allow rational adjustment of agents and dosing, and establishment of clinical follow-up strategies to facilitate "individualized" clinical management. PUBLIC HEALTH RELEVANCE: Although great promise has been shown for therapy of muscular dystrophy by gene and stem cell therapies, and steroids appear to improve physiological function, the complexity of the total disease process and the rapid progression to death in these patients begs for practical alternative strategies. The purpose of this proposal is to develop and evaluate new approaches to multiplexed therapeutics of muscular dystrophy based on recent progress in our laboratory that may bring targeted nanosystems to bear on diagnosis, therapy, and image- based management of muscular dystrophy. In this translational proposal, all of the required synthetic and analytical tools are at our disposal to conclusively determine if a targeted nanotechnology platform adds value to the management of experimental models of muscular dystrophy, which is a proposition that heretofore has never been tested.

描述（由申请人提供）：尽管通过基因和干细胞疗法对肌肉性营养不良的治疗表现出了很大的希望，并且类固醇似乎改善了生理功能，总疾病过程的复杂性以及这些患者在这些患者中的快速进展到死亡，以实践替代策略。该提案的目的是根据我们的实验室的最新进展，开发和评估新的肌肉营养不良疗法的新方法，这些治疗方法可能会使有针对性的纳米系统对诊断，治疗和基于图像的基于图像的肌肉性营养不良的治疗。在这项翻译建议中，所有必需的合成和分析工具均应最终确定目标的纳米技术平台是否为肌肉营养不良的实验模型的管理增加了价值，这是迄今为止从未测试过的命题。 该提案的总体假设是：基于纳米技术的方法为神经肌肉疾病的诊断和治疗性武术提供了独特而有价值的资产，并将以直接转化的方式为神经肌肉疾病的临床管理做出贡献。实验计划中的特定目的和概述的可交付成分或结果是：1）针对疾病的炎症性生物标志物的纳米颗粒的表述，以敏感，敏感性，并准确地报道肌肉性疾病的活性和演变，通过基于图像的启动肌肉症的读数，以使肌肉症的读数促进了较早的生物症，从而促进了型号的读物，从而促进了对型物的读者的读者，从而使生物症的读数是促进型物的循环效果。心脏和骨骼肌恶化； 2）与当前的治疗方法相比，开发了新的方法，用于重复将有效药物和遗传材料递送到靶向炎症部位，并降低毒性谱； 3）结合基于图像的疾病活动的读数与治疗性分娩结合，以合理地调整药物和剂量，并建立临床随访策略，以促进“个性化”的临床管理。 公共卫生相关性：尽管通过基因和干细胞疗法对肌肉营养不良的治疗表现出了巨大的希望，并且类固醇似乎可以改善生理功能，总疾病过程的复杂性以及这些患者的快速进展到死亡，乞求实用替代策略。该提案的目的是根据我们的实验室的最新进展来开发和评估肌营养不良症多路复用治疗的新方法，这些方法可能会使靶向纳米系统涉及诊断，治疗和基于图像的肌营养不良症治疗。在这项翻译建议中，所有必需的合成和分析工具均应最终确定目标的纳米技术平台是否为肌肉营养不良的实验模型的管理增加了价值，这是迄今为止从未测试过的命题。