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.
Public Health Relevance Statement: Project Narrative Tendinopathy is a common chronic tendon disorder, characterized by pain and impaired performance, and currently has no cure or effective treatments. Our preliminary studies suggest that a specific microRNA has therapeutic potential in healing diseased tendon tissue in rats. The proposed study will test the efficacy and safety of this microRNA in rodent and rabbit models of tendinopathy.
Project Terms: achilles tendon; Calcanean Tendon; Affect; Aging; Non-Steroidal Anti-Inflammatory Agents; NSAIDs; Non Steroidal Antiinflammatory Agents; Nonsteroidal Anti-Inflammatory Agents; Nonsteroidal Antiinflammatory Agents; Nonsteroidal Antiinflammatory Drug; non-steroidal anti-inflammatory drugs; non-steroidal antiinflammatory drugs; nonsteroidal anti-inflammatory drugs; Attention; Biological Assay; Assay; Bioassay; Biologic Assays; Cicatrix; Scars; Clinical Trials; Disease; Disorder; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Exhibits; Future; Gene Expression; Genes; Human; Modern Man; Hyaluronic Acid; Inflammation; Investments; New York; Painful; Pain; Pathology; Clinical Pathology; Pharmacokinetics; Drug Kinetics; Sham Treatment; sham therapy; Placebos; Predisposing Factor; Domestic Rabbit; Rabbits; Rabbits Mammals; Oryctolagus cuniculus; Common Rat Strains; Rat; Rats Mammals; Rattus; Development and Research; R & D; R&D; research and development; Ribonucleoside Phosphates; Ribonucleotides; Non-Polyadenylated RNA; RNA Gene Products; Ribonucleic Acid; RNA; Rodentia; Rodents Mammals; Rodent; Safety; Steroid Compound; Steroids; Swelling; Technology; Tendons; Tendon structure; Testing; Tissues; Body Tissues; Businesses; Mediating; Schedule; PKH 26; PKH26; biological adaptation to stress; reaction; crisis; stress response; stress; reaction; Apoptosis; Apoptosis Pathway; Programmed Cell Death; collagenase; Collagen Peptidase; Collagen-Degrading Enzyme; base; improved; Site; Chronic; Clinical; repaired; repair; Phase; Histologic; Histologically; Chemicals; Individual; inflammatory mediator; Inflammation Mediators; uptake; Therapeutic; scaffolding; scaffold; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; nuclease; Performance; pleiotropic effect; pleiotropy; pleiotropism; Animal Models and Related Studies; model of animal; model organism; Animal Model; Toxicities; Toxic effect; novel; Pathogenesis; Deterioration; Modeling; response; Adverse effects; MicroRNAs; Micro RNA; miRNA; miRNAs; Bio-Informatics; Bioinformatics; Molecular Interaction; Binding; Mesenchymal Progenitor Cell; Mesenchymal progenitor; Mesenchymal Stem Cells; Mediator; Mediator of Activation; Mediator of activation protein; Dose; Microarray-Based Analysis; microarray analyses; microarray technology; Microarray Analysis; Age-Years; Data; Rodent Model; trend; Modification; Therapeutic Effect; Tendinopathy; Tendinitis; Tendonitis; Pathway interactions; pathway; healing; efficacy evaluation; efficacy analysis; efficacy assessment; efficacy examination; evaluate efficacy; examine efficacy; Rupture; Outcome; Impairment; translational medicine; two-dimensional; 2-dimensional; novel therapeutics; new drug treatments; new drugs; new therapeutics; new therapy; next generation therapeutics; novel drug treatments; novel drugs; novel therapy; loss of function; commercial application; commercialization; aging population; aged population; population aging; novel therapeutic intervention; new therapeutic approach; new therapeutic intervention; new therapeutic strategies; new therapy approaches; novel therapeutic approach; novel therapeutic strategies; novel therapy approach; FDA approved; effective therapy; effective treatment; efficacy testing; pain behavior; phase 2 study; phase II study; tendon rupture; Formulation; exosome; mechanical properties; Injections; chronic inflammatory disease; searchable database; searchable data base; translational therapeutics; translational therapy
