miRNA drug for tendinopathy

项目摘要 肌腱病是一种在老年人中高度流行的肌腱疾病。它的特点是 肌腱退化，经常导致肌腱断裂，并与疼痛、肿胀和受损有关 性能。目前还没有治愈肌腱病的方法，迫切需要有效的治疗 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 初步研究证实miR-221-5p对啮齿动物肌腱病有治疗作用。 并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 这与肌腱病的发病机制有关。这个项目将检验化学修饰的假说 MIR-221-5P对肌腱病变有明显的缓解作用。第二阶段研究的重点将是提供 开发miR-221-5P作为FDA批准的用于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。 诱导肌腱病模型。在目标2中，我们将测定miR-221-5P对 兔肌腱病。成功完成拟议的研究将确定miR-221-5P为一种新药 用于治疗肌腱病和其他慢性炎症性疾病。

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.