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

基本信息

批准号：
7778154
负责人：
SAMUEL A WICKLINE
金额：
$ 34.2万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
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/7778154
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

项目摘要

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）：虽然通过基因和干细胞疗法治疗肌营养不良症显示出巨大的前景，并且类固醇似乎可以改善生理功能，但整个疾病过程的复杂性以及这些患者快速进展至死亡的情况令人担忧实用的替代策略。该提案的目的是根据我们实验室的最新进展，开发和评估肌营养不良症多重治疗的新方法，这些方法可能会将靶向纳米系统应用于肌营养不良症的诊断、治疗和基于图像的管理。在这个转化提案中，我们可以使用所有必需的合成和分析工具来最终确定目标纳米技术平台是否为肌营养不良症实验模型的管理增加价值，这是一个迄今为止从未经过测试的提案。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设备增添了独特且有价值的资产，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。具体目标中设想的和实验计划中概述的可交付成果或结果是： 1) 配制针对疾病炎症生物标志物的纳米颗粒，以非侵入性、灵敏且准确地报告肌营养不良症疾病过程的活动和演变基于图像读出对导致心肌和骨骼肌恶化的早期炎症变化具有病理生理学意义的选定分子生物标志物； 2）开发新方法，将强效药物和遗传物质重复递送至炎症目标部位，与目前的治疗方法相比，毒性降低； 3) 将基于图像的疾病活动读数与治疗递送相结合，以便合理调整药物和剂量，并建立临床随访策略，以促进“个体化”临床管理。公众健康相关性：虽然通过基因和干细胞疗法治疗肌营养不良症显示出巨大的前景，并且类固醇似乎可以改善生理功能，但这些患者的整个疾病过程的复杂性和快速进展至死亡的情况需要实用的替代方案策略。本提案的目的是根据我们实验室的最新进展，开发和评估肌营养不良症多重治疗的新方法，这些方法可能会将靶向纳米系统应用于肌营养不良症的诊断、治疗和基于图像的管理。在这个转化提案中，我们可以使用所有必需的合成和分析工具来最终确定目标纳米技术平台是否为肌营养不良症实验模型的管理增加价值，这是一个迄今为止从未经过测试的提案。