miRNA drug for tendinopathy

治疗肌腱病的 miRNA 药物

• 批准号: 10709649
• 负责人: David T Fung
• 金额: $ 56.9万
• 依托单位: NEW YORK/R&D/CTR/TRANSLATIONAL MED/THER
• 依托单位国家: 美国
• 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/10709649
• 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; Databases; Deterioration; Disease; Dose; Drug Kinetics; Equity; Exhibits; FDA approved; Formulation; Future; Gene Expression; Genes; Histologic; Human; Hyaluronic Acid; Impairment; Individual; Inflammation; Inflammation Mediators; Injections; Investments; Mediating; Mediator; 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; Predisposition; 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; 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; microRNA delivery; novel; novel therapeutic intervention; novel therapeutics; nuclease; pain behavior; phase 2 study; pleiotropism; repaired; research and development; response; scaffold; tendon rupture; translational medicine; translational therapeutics; trend; two-dimensional; uptake

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.

项目摘要 肌腱病是一种肌腱疾病，在老年人群中非常普遍。它的特点是 肌腱退化，往往导致肌腱断裂，并与疼痛，肿胀和受损 性能目前还没有治愈肌腱病的方法，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 初步研究发现，miR-221- 5 p在肌腱病的啮齿动物模型中表现出治疗作用， 并且可以至少部分地通过抑制促炎介质的表达来发挥其治疗效果 导致肌腱病的发病机制这个项目将测试化学修饰的假设， miR-221- 5 p对减轻肌腱病发挥增强的作用。第二阶段研究将重点提供 开发miR-221- 5 p作为FDA批准的用于治疗肌腱病的产品的关键证据。 在目的1中，我们将使用胶原酶确定miR-221- 5 p的化学制剂和处理条件。 肌腱病的诱导模型。在目标2中，我们将确定miR-221- 5 p对人乳腺癌的疗效和安全性。 兔肌腱病变。成功完成拟议的研究将确定miR-221- 5 p为新药 用于治疗肌腱病和其它慢性炎性疾病。