Optogenetic Pain Modulator for non-opioid chronic pain management

用于非阿片类慢性疼痛管理的光遗传学疼痛调节器

• 批准号: 10701510
• 负责人: Darryl Narcisse
• 金额: $ 32.79万
• 依托单位: OPSIN BIOTHERAPEUTICS INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10701510
• 关键词: Address; Adult; Affect; Age; Agreement; Animals; Area; Behavioral; Biological Assay; Biological Response Modifier Therapy; Case Study; Cells; Cessation of life; Characteristics; Chronic; Clinical; Clinical Pathology; Computer software; DNA; DNA analysis; Data Analyses; Deer; Development; Devices; Disease; Dose; Electrophysiology (science); Esthesia; Fentanyl; Goals; Histopathology; Hour; Human; Immunohistochemistry; Implant; Injury; Light; Lighting; Measurement; Mechanical Stimulation; Medical; Methodology; Methods; Morphine; Mus; Nature; Nerve; Neurologic; Neurons; Neurosciences; Operative Surgical Procedures; Opsin; Optics; Organ; Overdose; Oxycodone; Pain; Pain management; Pathway interactions; Peripheral Blood Mononuclear Cell; Pharmacologic Substance; Phase; Population; Primates; Production; Productivity; Quality of life; Regulatory Pathway; Research; Rewards; Risk Reduction; Rodent; Safety; Sampling; Specificity; Spinal; Spinal Cord; Spinal Ganglia; Structure; Symptoms; Syndrome; Technology; Therapeutic Effect; Tissues; Tramadol; Transfection; Transgenes; Translating; Translations; Vertebral column; Viral Vector; Virus; Withdrawal; addiction; adverse outcome; chronic pain; chronic pain management; commercialization; cost; effective therapy; experimental study; first-in-human; gene product; global health; hazard; implantable device; implantation; individualized medicine; inhibitory neuron; innovation; instrumentation; manufacture; nano; nanoGold; nanorod; neuroimaging; neuroregulation; non-opioid analgesic; novel; operation; opioid epidemic; optogenetics; pain behavior; pain model; pain perception; pain processing; pain sensation; painful neuropathy; personalized approach; personalized medicine; pre-clinical; programs; promoter; sex; success; systemic toxicity; therapy development; vector; wireless

Project Summary/Abstract: The most common noticeable symptom of disease and injury is pain. It can warn of danger or the need to treat a problem, however, when it becomes chronic, it can become debilitating. Chronic pain is estimated to affect up to a third of the global adult population(Majeed et al., 2018). Complications from pain treatment continue to cause addiction and injury (including death). Alternative methods for treating chronic pain (especially that recalcitrant to treatment) is critical to addressing both chronic pain itself and mitigating the hazards of long-term administration of current treatment methods. As is seen in the ongoing opioid crisis and the massive costs of chronic pain treatments, the consequences of untreated pain and treatment that lacks specificity can be dire. This results in a loss of quality of life and productivity. Optogenetics offers the possibility for both highly specific and customizable control of cellular activities, opening pathways for treatments that reduce risks via cellular specificity while also allowing personalized therapies. Currently, the most common opsins require an excessive amount of power to be activated or are sensitive to wavelengths of light that can damage tissues, thus limiting their utility in medical treatments. To address these limitations, we have developed a unique sensitive opsin and a stimulation device which can provide targeted and tailored activation of the opsin. Multi- Characteristic Opsin (MCO) can be delivered to neurons involved in the sensation and processing of pain and stimulated as needed to minimize pain perception. Preliminary research has established the baseline parameters for optogenetic modulation of pain, and our continued research establishes the value and safety of this approach for pain management. To further the characterization and optimization of our approach, we plan to perform the following aims: Aim 1: Optimize OPM optical delivery and transdermal/wireless optogenetic stimulation device. Aim 2: Optimize the efficacy of the Modulator and Opsin construct for safe long-term treatment of pain. Successful development holds the promise to revolutionize pain therapy through a highly specific, personalized approach to pain mitigation with reduced hazards and enhanced rewards. This novel optogenetic treatment could be applied to several chronic pain syndromes with potential applications for other neurological conditions.

项目摘要/摘要： 最常见的疾病和伤害症状是疼痛。它可以警告危险或 但是，需要治疗问题，当它变得慢性时，它可能会变得虚弱。慢性的 据估计，疼痛会影响全球成年人口的三分之一（Majeed等，2018）。 疼痛治疗的并发症继续引起成瘾和伤害（包括死亡）。 治疗慢性疼痛的替代方法（尤其是治疗的顽固疼痛）对于 解决慢性疼痛本身，并减轻长期给药的危害 当前的治疗方法。正如正在进行的阿片类药物危机和巨大成本所示 慢性疼痛治疗，未经治疗的疼痛和缺乏特异性的后果 可能是可怕的。这会导致生活质量和生产力的损失。光遗传学提供 高度特异性和可定制的细胞活动控制的可能性，开放途径 用于通过细胞特异性降低风险的治疗，同时允许个性化疗法。 目前，最常见的Opsins需要激活或 对可能损坏组织的光波长敏感，从而限制了它们在医疗中的效用 治疗。为了解决这些局限性，我们开发了一种独特的敏感OPSIN和 刺激装置可以提供靶向和定制的OPSIN激活。多- 特征性蛋白（MCO）可以传递给参与感觉和加工的神经元 疼痛并根据需要刺激以最大程度地减少疼痛感。初步研究 建立了用于疼痛光学调节的基线参数，我们的续 研究确定了这种方法对疼痛管理的价值和安全性。进一步 表征和优化我们的方法，我们计划执行以下目的： AIM 1：优化OPM光学输送和透皮/无线光遗传刺激 设备。 AIM 2：优化调制器和Opsin构建体的功效，以确保长期安全 治疗疼痛。 成功的发展有望通过高度具体的， 个性化缓解疼痛的方法，危害减少和增强的奖励。这本小说 光遗传学治疗可以应用于具有潜在的几种慢性疼痛综合症 用于其他神经系统疾病的应用。