More than 25 million Americans suffer from chronic pain. In recent decades, due to the lack of other effectivetreatments, there has been an overreliance on opioids despite their poor ability to improve function. This hasbeen contributing to a significant and alarming epidemic of opioid overdose deaths and addictions. Osteoarthritis (OA) is the most common degenerative joint disease, affecting 34% of people over 65 yearsof age and nearly 27 million people in the United States. The main symptom of OA patients is pain following asignificant loss of the articular cartilage. As there are currently no disease modifying agents, analgesics are themainstay of treatment but often deliver limited efficacy and can induce serious injury and death. We have designed and optimized a protein-based and long-acting analgesic. The therapy will deliver robustefficacy without causing significant side effects as it preferably targets to inflamed tissues and only activatesperipheral ïï and ï«-opioid receptors on sensory neurons or immune cells. In the proposed studies, we willevaluate the dose-response of the proprietary drug candidate in a well-established rat model of OA pain. Wealso will determine the potential side effects in the Functional Observational Battery assays in healthy rats,along with a general toxicological screen of major organ systems. The long-term goal is to develop the drugcandidate as a safe and effective analgesic therapy. Weekly or bi-weekly dosing will provide sustained painrelief for OA pain patients without addiction and other adverse side effects. Principal Investigator/Program Director (Last, First, Middle: Ridong Chen
Narrative
We will determine whether a novel peripherally acting analgesic will reverse osteoarthritic pain without side
effects in a well-established animal model of joint pain. Blood Vessels ; vascular ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Cartilage ; Cartilaginous Tissue ; articular cartilage ; Cells ; Cell Body ; Clinical Trials ; Constipation ; Cessation of life ; Death ; Disease ; Disorder ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Dynorphins ; Endorphins ; Escherichia coli ; E coli ; E. coli ; Exhibits ; Goals ; Half-Life ; Human ; Modern Man ; Ibuprofen ; Motrin ; Interleukin-2 ; Co-Stimulator ; Costimulator ; Epidermal Thymocyte Activating Factor ; IL-2 ; IL2 Protein ; Interleukin 2 ; Interleukin 2 Precursor ; Interleukin II ; Interleukine 2 ; Interleukine 2 Precursor ; Interleukine II ; Lymphocyte Mitogenic Factor ; Mitogenic Factor ; T cell growth factor ; T-Cell Growth Factor ; T-Cell Stimulating Factor ; Thymocyte Stimulating Factor ; Joints ; Molecular Weight ; Morphine ; Infumorph ; Kadian ; MS Contin ; MSir ; Morphia ; Oramorph ; Oramorph SR ; Roxanol ; Statex SR ; Mutation ; Genetic Alteration ; Genetic Change ; Genetic defect ; genome mutation ; Afferent Neurons ; Sensory Cell Afferent Neuron ; Sensory Neurons ; Neuropeptides ; Degenerative polyarthritis ; Degenerative Arthritis ; Osteoarthritis ; Osteoarthrosis ; degenerative joint disease ; hypertrophic arthritis ; osteoarthritic ; Pain ; Painful ; Intractable Pain ; Refractory Pain ; intractable pain syndrome ; Patients ; Plasma ; Blood Plasma ; Plasma Serum ; Reticuloendothelial System, Serum, Plasma ; Proteins ; Quality of life ; QOL ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Opioid Receptor ; Opiate Receptors ; Interleukin 2 Receptor ; High Affinity Interleukin-2 Receptor ; IL-2 Receptors ; IL2 Receptors ; T-Cell Growth Factor Receptors ; TCGF Receptors ; Recombinant Proteins ; Serum Albumin ; Streptozocin ; STZ ; Streptozotocin ; Zanosar ; Syndrome ; Regulatory T-Lymphocyte ; Treg ; regulatory T-cells ; Tissues ; Body Tissues ; Toxicology ; United States ; Work ; Mediating ; chronic pain ; Chimeric Proteins ; Chimera Protein ; Fusion Protein ; Injury ; injuries ; base ; Replacement Arthroplasty ; Arthroplasty ; Joint Prosthesis Implantation ; joint arthroplasty ; joint replacement ; Peripheral ; Chronic ; Phase ; endogenous opioids ; endogenous opiate ; Aldesleukin ; Proleukin ; Recombinant Human IL-2 ; Recombinant Human Interleukin-2 ; Renal clearance function ; renal clearance ; inflammatory pain ; Opioid ; Opiates ; analog ; Solid Neoplasm ; Solid Tumor ; No-Observed-Adverse-Effect Level ; NOAEL ; Therapeutic ; Attenuated ; Inflammatory ; sedation ; Sedation procedure ; Absence of sensibility to pain ; Feels no pain ; No sensitivity to pain ; analgesia ; Absence of pain sensation ; Medial Menisci ; Meniscus Medialis ; Medial meniscus structure ; programs ; Immunes ; Immune ; neuropathic ; Neuropathy ; subdermal ; subcutaneous ; Organ System ; body system ; Tumor Tissue ; gastrointestinal ; celebrex ; celecoxib ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; American ; molecular size ; hydrophilicity ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Structure ; Therapeutic Index ; Immunomodulation ; immune modulation ; immune regulation ; immunologic reactivity control ; immunomodulatory ; immunoregulatory ; immunoregulation ; novel ; Tylenol ; Modeling ; response ; Adverse effects ; Surgical Models ; T-Cell Proliferation ; T-Cell Activation ; Hedgehog (Hh) signal transduction pathway ; hedgehog signaling ; hedgehog signaling pathway ; hh signaling pathway ; smoothened signaling pathway ; Molecular Interaction ; Binding ; preventing ; prevent ; CD25 ; IL2R ; IL2RA ; TCGFR ; IL2RA gene ; COX-2 ; COX2 ; PGHS-2 ; PHS-2 ; PTGS2 ; hCOX-2 ; PTGS2 gene ; Dose ; Symptoms ; Age-Years ; Data ; Mammalian Cell ; Receptor Signaling ; Principal Investigator ; painful neuropathy ; neuropathic pain ; neurobehavioral ; immunogenicity ; design ; designing ; clinical efficacy ; chronic constriction injury ; improved functioning ; diabetic rat ; Rat model of diabetes ; diabetic rat model ; protective effect ; innovation ; innovate ; innovative ; Impairment ; addiction ; addictive disorder ; type I diabetic ; type 1 diabetic ; effective therapy ; effective treatment ; preclinical safety ; pre-clinical safety ; drug candidate ; overdose death ; overdose fatalities ; targeted treatment ; targeted drug therapy ; targeted drug treatments ; targeted therapeutic ; targeted therapeutic agents ; targeted therapy ; pain symptom ; painful symptom ; opioid epidemic ; opiate crisis ; opioid crisis ; opioid mortality ; opiate deaths ; opiate mortality ; opioid deaths ; opioid overdose death ; opioid related death ; pain patient ; pain relief ; relieve pain ; osteoarthritis pain ; osteoarthritis associated pain ; Opioid agonist ; Opiate agonist ; Opiate receptor agonist ; Opioid receptor agonist ; side effect ; effector T cell ; Teff cell ; Autoimmune ; Acetaminophen ; APAP ; Acetamidophenol ; Acetominophen ; Hydroxyacetanilide ; Paracetamol ; Acetates ; Affect ; Analgesics ; Analgesic Agents ; Analgesic Drugs ; Analgesic Preparation ; Anodynes ; Antinociceptive Agents ; Antinociceptive Drugs ; pain killer ; pain medication ; pain reliever ; painkiller ; 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 ; Apnea ; Arthralgia ; Joint Pain ; Binding Sites ; Combining Site ; Reactive Site ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ;
