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miRNA drug for tendinopathy

治疗肌腱病的 miRNA 药物

基本信息

批准号：
10603377
负责人：
David T Fung
金额：
$ 73.74万
依托单位：
NEW YORK/R&D/CTR/TRANSLATIONAL MED/THER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10603377
关键词：
Adverse effects Affect Age-Years Aging Animal Model Apoptosis Attention Binding Bioinformatics Biological Assay Businesses Chemicals Chronic Cicatrix Clinical Clinical Pathology Clinical Trials Data Deterioration Disease Dose Drug Kinetics Exhibits FDA approved Formulation Future Gene Expression Genes Histologic Human Hyaluronic Acid Impairment Individual Inflammation Inflammation Mediators Injections Investments Mediating Mediator of activation protein Mesenchymal Stem Cells MicroRNAs Microarray Analysis Modeling Modification New York Non-Steroidal Anti-Inflammatory Agents Operative Surgical Procedures Oryctolagus cuniculus Outcome PKH 26 Pain Pathogenesis Pathology Pathway interactions Performance Pharmaceutical Preparations Phase Placebos Predisposing Factor RNA Rattus Ribonucleotides Rodent Rodent Model Rupture Safety Schedule Site Steroids Swelling Technology Tendinopathy Tendon structure Testing Therapeutic Therapeutic Effect Tissues Toxic effect achilles tendon aging population base biological adaptation to stress chronic inflammatory disease collagenase commercial application commercialization effective therapy efficacy evaluation efficacy testing exosome healing improved loss of function mechanical properties novel novel therapeutic intervention novel therapeutics nuclease pain behavior phase 2 study pleiotropism repaired research and development response scaffold searchable database tendon rupture translational medicine translational therapeutics trend two-dimensional uptake

项目摘要

Project Summary Tendinopathy is a tendon disorder that is highly prevalent in the aged population. It is characterized by tendon deterioration that often leads to tendon rupture, and is associated with pain, swelling and impaired performance. There is currently no cure for tendinopathy and an urgent need for effective treatments for tendinopathy. The technology to be developed is microRNA (miR)-221-5p for the treatment of tendinopathy. Our preliminary studies identified that miR-221-5p exhibited a therapeutic effect in a rodent model of tendinopathy and may exert its therapeutic effect, at least in part, by suppressing expression of pro-inflammatory mediators that contribute to the pathogenesis of tendinopathy. This project will test the hypothesis that chemically modified miR-221-5p exerts an enhanced effect on mitigating tendinopathy. The Phase II study will focus on providing critical evidence towards developing miR-221-5p as an FDA-approved product for the treatment of tendinopathy. In Aim 1, we will determine the chemical formulation and treatment condition of miR-221-5p using a collagenase- induced model of tendinopathy. In Aim 2, we will determine the efficacy and safety of miR-221-5p on tendinopathy in rabbits. Successful completion of the proposed studies will identify miR-221-5p as a new drug for the treatment of tendinopathy and other chronic inflammatory diseases.

项目概要肌腱病是一种在老年人群中非常普遍的肌腱疾病。其特点是肌腱退化常常导致肌腱断裂，并伴有疼痛、肿胀和受损表现。目前肌腱病尚无治愈方法，迫切需要有效的治疗方法肌腱病。待开发的技术是用于治疗肌腱病的 microRNA (miR)-221-5p。我们的初步研究发现 miR-221-5p 在啮齿动物肌腱病模型中表现出治疗作用并且可能至少部分通过抑制促炎介质的表达来发挥其治疗作用有助于肌腱病的发病机制。该项目将检验化学修饰的假设 miR-221-5p 对减轻肌腱病具有增强作用。第二阶段研究将重点提供开发 miR-221-5p 作为 FDA 批准的治疗肌腱病的产品的关键证据。在目标 1 中，我们将使用胶原酶确定 miR-221-5p 的化学配方和处理条件肌腱病诱导模型。在目标 2 中，我们将确定 miR-221-5p 对兔子的肌腱病。成功完成拟议研究将确定 miR-221-5p 为新药用于治疗肌腱病和其他慢性炎症性疾病。