NEW YORK R & D CENTER FOR TRANSLATIONAL MEDICINE & THERAPEUTICS INC — Department of Health and Human Services SBIR Phase II: NIA

Description

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 Randamp;D towards initiating clinical trials in humans. 1Project Narrative Tendinopathy is a common chronic tendon disorder, characterized by pain and impaired performance, and currently has no cure or effective treatments. Our Phase I studies showed that exosomes, nanosized extracellular vesicles secreted by mesenchymal stem cells, when grown on the TenoGen scaffold, a novel 3- dimensional scaffold, exert therapeutic efficacy in healing diseased tendon tissue in rats. The proposed study will test the efficacy and safety of the intended clinical product in an immunodeficient rodent model, and of an analogous product in a rabbit model via autologous and allogeneic treatment.