Developing EXP-1801 as an imaging agent to quantify pain and analgesia

开发 EXP-1801 作为成像剂来量化疼痛和镇痛

• 批准号: 9909162
• 负责人: BRAXTON NORWOOD
• 金额: $ 40.77万
• 依托单位: EXPESICOR, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909162
• 关键词: Absence of pain sensation; Acute; Acute Disease; Acute Pain; Address; Adult; American; Analgesics; Animal Model; Animals; Area; Basic Science; Behavioral; Binding; Biological Assay; Caring; Chronic; Clinical; Clinical Trials; Cognitive; Communication; Data; Descriptor; Detection; Development; Diagnostics Research; Disease; Economic Burden; Epidemic; Evaluation; Evolution; Exhibits; Goals; Human; Image; Imaging technology; Infrastructure; Injury; Knowledge; Lidocaine; Ligands; Ligation; Malignant Neoplasms; Measurement; Measures; Medical Research; Modeling; Morphine; Nature; Nerve Tissue; Neurons; Operative Surgical Procedures; Opioid; Pain; Pain Measurement; Pain management; Pathologic; Patient Self-Report; Patients; Persons; Phase; Population; Positron-Emission Tomography; Rattus; Recording of previous events; Reporting; Research; Resources; Rodent; Sample Size; Severities; Signal Transduction; Sodium Channel; Spinal; Spinal Cord; Spinal nerve structure; Surveys; Tactile; Target Populations; Technology; Testing; Time; Tissues; Unconscious State; United States National Institutes of Health; Western Blotting; addiction; allodynia; base; chronic pain; clinical pain; cost; density; design; drug development; efficacy study; experience; experimental study; human subject; imaging agent; improved; in vivo; injured; molecular imaging; nervous system disorder; nonhuman primate; novel; novel therapeutics; opioid abuse; overtreatment; pain behavior; pain model; pain patient; pain reduction; pain signal; painful neuropathy; phase 2 study; pre-clinical; preclinical study; research facility; spinal cord imaging; standard of care; targeted treatment; therapy development; tool; transmission process; voltage

Summary/Abstract There are currently no tools available that can objectively measure pain. Historically, pain in humans has been measured using subjective ratings to determine presence and severity. In animal models, pain is measured by semi-quantitative assays that rely on the observation of pain behaviors. Though useful, the inherently subjective nature of these measures has hampered both research and treatment efforts. Simply put, inaccurate pain measurement leads to inaccurate pain management. Overtreatment and addiction to pain medications are a continuing epidemic in the U.S. The estimated economic burden of chronic pain is estimated to exceed $600 billion. One advantage of an objective pain measuring technology is cost reduction. The average cost to treat a chronic or neuropathic pain patient is $19,000 per year. These costs are exaggerated because many patients have inadequately managed pain, which requires disproportionately more resources. A significant portion of these costs go to patients who are not experiencing substantial pain; e.g. those who abuse opioids. Another area where costs could be significantly reduced is in drug development. The average pain clinical trial cost is around $71 million. The use of a pain imaging technology would allow for objective efficacy data (both pre-clinically and in clinical trials), and reduce costs by enabling smaller sample sizes due to more homogeneous populations; i.e. with a particular “pain signal,” and more accurate measurement of analgesic effects. We recently invented a novel positron emission tomography (PET) imaging agent that we developing as a tool to address these issues in pain care and therapy development. Although the ability of PET to detect pathological changes for (early) disease detection is widely used in cancer and neurological diseases, it has not yet been used for pain indications. We have tested this molecule in healthy rats and non-human primates and found a strong signal to background ratio in nerve tissue. Our ultimate goals are: 1) to change the evaluation of (experimental) pain therapies, and 2) the standard of care in pain assessment through molecular imaging. The proposed study is designed to determine the feasibility of our imaging agent to objectively measure pain in rodents. This will set the stage for a Phase II study that further develops this agent into a tool for quantifying pain/analgesia.

摘要/摘要 目前还没有可用的工具可以客观地测量人类的疼痛。 使用主观评分来确定疼痛的存在和严重程度。 依赖于疼痛行为观察的半定量测定虽然有用，但本质上是有用的。 简而言之，这些措施的性质阻碍了研究和治疗工作。 疼痛测量导致不准确的疼痛管理和止痛药成瘾。 美国持续流行，慢性疼痛的经济负担估计超过 600 美元 客观疼痛测量技术的一个优点是降低治疗成本。 慢性或神经性疼痛患者每年的费用为 19,000 美元，因为许多患者的费用被夸大了。 疼痛管理不充分，这需要不成比例的更多资源。 这些费用支付给没有经历严重疼痛的患者，例如滥用阿片类药物的患者。 另一个可以显着降低成本的领域是药物开发。 成本约为 7100 万美元，使用疼痛成像技术可以获得客观的疗效数据（两者）。 临床前和临床试验中），并通过使用更小的样本量来降低成本 同质人群；即具有特定的“疼痛信号”，以及更准确的镇痛测量 影响。 我们最近发明了一种新型正电子发射断层扫描 (PET) 成像剂，我们将其开发为一种工具 尽管 PET 具有检测能力，但仍可以解决疼痛护理和治疗开发中的这些问题。 用于（早期）疾病检测的病理变化广泛应用于癌症和神经系统疾病，它具有 我们已经在健康大鼠和非人类灵长类动物中测试了这种分子。 并发现神经组织中有很强的信号背景比。我们的最终目标是：1）改变 （实验性）疼痛疗法的评估，以及 2）通过分子生物学评估疼痛的护理标准 成像。 拟议的研究旨在确定我们的显像剂客观测量疼痛的可行性 这将为第二阶段研究奠定基础，进一步将该药物开发成量化工具。 疼痛/镇痛。