A novel product for tendinopathy treatment

一种治疗肌腱病的新产品

基本信息

批准号：
10264118
负责人：
David T Fung
金额：
$ 83.16万
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：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10264118
关键词：
3-Dimensional Address Adipose tissue Adverse effects Allogenic Animal Model Animals Attention Autologous Biological Biological Response Modifier Therapy Businesses Chronic Cicatrix Clinical Clinical Research Clinical Trials Cultured Cells Data Deterioration Disease Dose Evaluation FDA approved Fiber Future Harvest Histopathology Human Impairment Inflammatory Infiltrate Investigation Investments Legal patent Mesenchymal Stem Cells Modeling Morbidity - disease rate New York Nude Rats Operative Surgical Procedures Oryctolagus cuniculus Outcome Pain Pathology Performance Rattus Rodent Model Rupture Safety Schedule Silk Site Swelling Tendinopathy Tendon structure Testing Therapeutic Therapeutic Effect Tissues Toxic effect Treatment Efficacy Treatment Protocols United States aged base cell age cell type collagenase commercial application commercialization effective therapy efficacy evaluation efficacy testing exosome extracellular vesicles healing immunogenic improved mechanical properties nanosized novel pain behavior pain relief pain symptom phase 1 study phase 2 study pre-clinical repaired research and development scaffold stem stem cells tendon rupture therapeutically effective translational medicine

项目摘要

Project Summary Tendinopathy is a tendon disorder 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. Therefore, there is an urgent need for effective treatments for tendinopathy. Exosomes are specialized membranous nano-sized extracellular vesicles derived from endocytic compartments that are released by many cell types. Our initial discovery was that exosomes secreted from tendon derived stem/progenitor cells (TSPCs) cultured on a novel scaffold, when injected into a tendinopathic tendon, mitigated pathology and pain in a rat tendinopathy model. We therefore designated the exosomes derived from MSCs cultured on this novel scaffold as “TenoGen,” and established a project to develop TenoGen as an FDA-approved biologic for tendinopathy treatment. In our Phase I study, we found that the exosomes derived from human adipose-derived stem cells (ADSCs) exert an efficacy on tendinopathy that was comparable to that derived from TSPCs, and revealed that TenoGen produced by TSPCs or ADSCs from aged donors exerts a therapeutic effect on tendinopathy. Furthermore, we examined and found no general signs of toxicity in the rats treated with TenoGen. These exciting results in the Phase I study encouraged us to further test our hypothesis that TenoGen exerts a therapeutic effect in mitigating tendinopathy pathology and relieving tendinopathy-related pain and symptoms with no or minimal adverse effects. The Phase II study will focus on providing further critical evidence towards developing TenoGen as an FDA-approved biologic for the autologous or allogeneic treatment of tendinopathy. We will first determine the efficacy and safety of TenoGen derived from human ADSCs in a tendinopathy model in nude rats (Aim 1). Specifically, we will first determine the optimal dose and dosing schedule of TenoGen and determine the efficacy of TenoGen on pathology of tendinopathy. By using the selected optimal dose and optimal dosing schedule. We will further determine efficacies of TenoGen on improving the mechanical properties of the diseased tendon, and on relieving pain and behaviors related to tendinopathy. Furthermore, in alignment with the regulatory requirements for TenoGen as a novel biologic, the safety of human TenoGen will be evaluated in this immunodeficient animal model. In Aim 2, we will determine the efficacy and safety of TenoGen for autologous and allogeneic treatment in a tendinopathy model in rabbits, which allows for the evaluation of TenoGen on tendinopathy in a mid-sized animal model that closely mimics the future treatment protocol in humans. Successful completion of these studies will provide critical preclinical evidence to support the efficacy and safety of TenoGen as a biologic for the allogeneic treatment of tendinopathy. The data will be instrumental for a FDA IND application, and the future R&D towards initiating clinical trials in humans. 1

项目概要肌腱病是一种肌腱疾病，其特征是肌腱退化，常常导致肌腱断裂，并且与疼痛、肿胀和功能受损有关，目前尚无法治愈肌腱病。因此，迫切需要针对肌腱病的有效治疗。膜状纳米大小的细胞外囊泡，源自许多细胞释放的内吞室我们最初的发现是肌腱来源的干/祖细胞（TSPC）分泌的外泌体。在新型支架上培养，当注射到肌腱病变肌腱时，可减轻大鼠的病理和疼痛因此，我们将源自在这种新型支架上培养的 MSC 的外泌体命名为肌腱病模型。命名为“TenoGen”，并建立了一个项目，将 TenoGen 开发为 FDA 批准的肌腱病生物制剂在我们的第一阶段研究中，我们发现源自人类脂肪干细胞的外泌体。 (ADSC) 对肌腱病的疗效与 TSPC 相当，并表明由老年捐献者的 TSPC 或 ADSC 产生的 TenoGen 对肌腱病具有治疗作用。此外，我们检查并发现用 TenoGen 治疗的大鼠没有一般毒性迹象。第一阶段研究的令人兴奋的结果鼓励我们进一步检验我们的假设，即 TenoGen 发挥了减轻肌腱病病理和缓解肌腱病相关疼痛和症状的治疗效果第二阶段研究将重点提供进一步的关键证据。开发 TenoGen 作为 FDA 批准的生物制剂，用于自体或同种异体治疗肌腱病。我们将首先确定源自人类 ADSC 的 TenoGen 在肌腱病模型中的有效性和安全性具体来说，我们将首先确定 TenoGen 和的最佳剂量和给药方案。通过使用选定的最佳剂量和最佳剂量来确定 TenoGen 对肌腱病病理学的疗效。我们将进一步确定 TenoGen 在改善机械性能方面的功效。患病肌腱，以及缓解与肌腱病相关的疼痛和行为。此外，与由于 TenoGen 作为一种新型生物制剂的监管要求，人类 TenoGen 的安全性将在在目标 2 中，我们将确定 TenoGen 对这种免疫缺陷动物模型的有效性和安全性。在兔子肌腱病模型中进行自体和同种异体治疗，可以评估 TenoGen 在中型动物模型中研究肌腱病，该模型非常模仿未来的治疗方案成功完成这些研究将为支持疗效提供关键的临床前证据。 TenoGen 作为同种异体治疗肌腱病的生物制剂的安全性和安全性这些数据将很有帮助。用于 FDA IND 申请，以及未来启动人体临床试验的研发。 1