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

Description

PROJECT SUMMARYThis study aims to prove the concept and feasibility that oral administration of Ea product formulated from a combination of generally regarded as safe compoundsGRASexerts therapeutic efficacy on tendinopathyTendinopathy is a common chronic tendon disorder that affects young athletes andof individuals overyears oldIt is characterized by painswellingloss of functionand impaired performance and often leads to tendon ruptureThere is currently no cure for tendinopathySpontaneous repair or treatment typically leads to scar formationresulting in a weakened tissue with reduced function and mechanical properties that may ultimately rupture with further useCITEDCbp pInteracting Transactivator with ED rich tailis a transcriptional regulator which plays a critical role in tendon stem progenitor cellTSPCsurvivalPreliminary data strongly suggest implanting TSPCs with enhanced levels of CITEDinto a collagenase induced tendinopathic Achilles tendon mitigated disease progressionrelieved tendinopathy related painand improved tendon mechanical propertiesA drug that enhances CITEDexpression and is safe for a long term use is of particular importance and is highly desiredEwas identified based on a drug screening strategy from a pool of GRAS compoundsOur preliminary studies show Eacts to induce the expression of CITEDand suppresses expression of a spectrum of genes including pro inflammatory and catabolic mediators and altered oxidative stress responses both in vitro and in vivoImportantlyoral administration of Ein a rat collagenase induced tendinopathy model mitigated disease progression and relieved tendinopathy related painproviding evidence that led us to hypothesize that Etreatment slows tendinopathy progressionrelieves pain of tendinopathyand improves mechanical properties of the diseased tendonsIn the proposed Phase I studieswe will test this hypothesis using the overuse induced tendinopathy model in rats by carrying out a study assessinghistologic and semi quantitative analysis of tissue and cellular morphology including number and morphology of the tenocytescell and collagen matrix alignmentexpression of tenophenotypic related genesmagnetic resonance imagingmechanical property testingandpain and other behavioral evaluationsThe positive outcome will be determined quantitatively when the results of these assays showEtreated tendons are significantly improved vs vehicle controlspandltandEtreated tendons vs na ve control groups are not significantly differentpandgtThe study will provide feasibility for the Phase II studies that are planned to provide further evidence for Eas a drug for tendinopathy using a large animal modelUpon successful completion of Phase I and II studieswe will file an Investigational New Drug application and carry out clinical trials focusing on the most common sites of tendinopathyThese trials will contingently be carried out at Montefiore Medical Centerwith an aim to market Eas a drug for tendinopathy treatment PROJECT NARRATIVE Tendinopathy is a common chronic tendon disordercharacterized by pain and impaired performanceoften leads to tendon ruptureand it currently has no cure or effective treatmentsThis study aims to prove the concept and provide the feasibility that oral administration of a potential drugcomposed of a novel combination of generally regarded as safe compoundsexerts therapeutic efficacy on tendinopathy by slowing disease progressionmitigating painand improving tendon mechanical properties using an overuse induced tendinopathy model in rats