Peripherally Acting Analgesic for Osteoarthritis Pain

用于治疗骨关节炎疼痛的外周镇痛药

• 批准号: 10249564
• 负责人: RIDONG CHEN
• 金额: $ 25.96万
• 依托单位: APT THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-05 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249564
• 关键词: Absence of pain sensation; Acetaminophen; Acetates; Adverse effects; Affect; Afferent Neurons; Age-Years; Aldesleukin; American; Analgesics; Animal Model; Apnea; Arthralgia; Attenuated; Autoimmune; Binding; Binding Sites; Biological Assay; Blood Vessels; Cartilage; Cells; Cessation of life; Chimeric Proteins; Chronic; Clinical Trials; Constipation; Data; Degenerative polyarthritis; Disease; Dose; Dynorphins; Endorphins; Escherichia coli; Exhibits; Goals; Half-Life; Human; IL2RA gene; Ibuprofen; Immune; Impairment; Inflammatory; Injury; Interleukin 2 Receptor; Interleukin-2; Intractable Pain; Joints; Malignant Neoplasms; Mammalian Cell; Medial meniscus structure; Mediating; Modeling; Molecular Weight; Morphine; Mutation; Neuropathy; Neuropeptides; No-Observed-Adverse-Effect Level; Non-Steroidal Anti-Inflammatory Agents; Operative Surgical Procedures; Opioid; Opioid Receptor; Opioid agonist; PTGS2 gene; Pain; Patients; Peripheral; Pharmaceutical Preparations; Phase; Plasma; Principal Investigator; Proteins; Quality of life; Rattus; Receptor Signaling; Recombinant Proteins; Regulatory T-Lymphocyte; Renal clearance function; Replacement Arthroplasty; Sedation procedure; Serum Albumin; Solid Neoplasm; Streptozocin; Structure; Surgical Models; Symptoms; Syndrome; T-Cell Activation; T-Cell Proliferation; Therapeutic; Therapeutic Index; Tissues; Toxicology; Tumor Tissue; Tylenol; United States; Work; addiction; analog; articular cartilage; base; body system; celecoxib; chronic constriction injury; chronic pain; clinical efficacy; design; diabetic rat; drug candidate; effective therapy; effector T cell; endogenous opioids; gastrointestinal; hydrophilicity; immunogenicity; immunoregulation; improved functioning; inflammatory pain; innovation; molecular size; neurobehavioral; novel; opioid epidemic; opioid mortality; osteoarthritis pain; overdose death; pain patient; pain relief; pain symptom; painful neuropathy; preclinical safety; prevent; programs; protective effect; response; side effect; smoothened signaling pathway; subcutaneous; targeted treatment; type I diabetic

Principal Investigator/Program Director (Last, First, Middle: Ridong Chen Project Summary More than 25 million Americans suffer from chronic pain. In recent decades, due to the lack of other effective treatments, there has been an overreliance on opioids despite their poor ability to improve function. This has been 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 years of age and nearly 27 million people in the United States. The main symptom of OA patients is pain following a significant loss of the articular cartilage. As there are currently no disease modifying agents, analgesics are the mainstay 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 robust efficacy without causing significant side effects as it preferably targets to inflamed tissues and only activates peripheral  and -opioid receptors on sensory neurons or immune cells. In the proposed studies, we will evaluate the dose-response of the proprietary drug candidate in a well-established rat model of OA pain. We also 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 drug candidate as a safe and effective analgesic therapy. Weekly or bi-weekly dosing will provide sustained pain relief for OA pain patients without addiction and other adverse side effects.

主要研究者/项目负责人（末、中、首：陈日东 项目摘要 超过2500万美国人患有慢性疼痛。近几十年来，由于缺乏有效的 在治疗方面，人们过度依赖阿片类药物，尽管它们改善功能的能力很差。这 一直导致阿片类药物过量死亡和成瘾的严重和令人震惊的流行。 骨关节炎（OA）是最常见的退行性关节疾病，影响34%的65岁以上的人 年龄和近2700万人在美国。OA患者的主要症状是疼痛， 关节软骨严重受损由于目前没有疾病修饰剂，镇痛剂是治疗的主要药物。 治疗的支柱，但往往提供有限的疗效，并可能导致严重的伤害和死亡。 我们设计并优化了一种基于蛋白质的长效镇痛剂。该疗法将提供强大的 因为它优选靶向发炎组织，并且仅激活 感觉神经元或免疫细胞上的外周阿片受体和β-阿片受体。在建议的研究中，我们会 评价专利候选药物在成熟的OA疼痛大鼠模型中的剂量反应。我们 还将在健康大鼠的功能观察组合试验中确定潜在的副作用， 沿着主要器官系统的一般毒理学筛查。长期目标是开发这种药物 作为一种安全有效的镇痛治疗的候选药物。每周一次或每两周一次给药将提供持续疼痛 缓解OA患者疼痛，无成瘾等不良副作用。