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： 疾病和伤害最常见的明显症状是疼痛。它可以警告危险或 需要治疗的问题，然而，当它变成慢性时，它可能会变得虚弱。慢性 据估计，疼痛影响全球三分之一的成年人口(Majeed等人，2018年)。 疼痛治疗的并发症继续导致上瘾和受伤(包括死亡)。 治疗慢性疼痛的替代方法(特别是那些顽固的治疗方法)对 既能解决慢性疼痛本身，又能减轻长期服用 目前的治疗方法。正如正在进行的阿片类药物危机和 慢性疼痛治疗、未经治疗的疼痛的后果以及缺乏特异性的治疗 可能会很可怕。这会导致生活质量和生产力的下降。光遗传学提供了 可能对细胞活动进行高度特定和可定制的控制，打开途径 用于通过细胞特异性降低风险的治疗，同时也允许个性化治疗。 目前，最常见的眼球蛋白需要过多的能量才能激活或 对可能损害组织的光的波长敏感，从而限制了它们在医学上的用途 治疗。为了解决这些限制，我们开发了一种独特的敏感眼球蛋白和一种 刺激装置，可以提供有针对性和量身定做的视蛋白激活。多个- 特征视蛋白(MCO)可以传递给参与感觉和加工的神经元 并根据需要进行刺激，以最大限度地减少痛感。初步研究已经 建立了疼痛的光遗传调制的基线参数，我们继续 研究确定了这种方法对于疼痛管理的价值和安全性。为了进一步发展 为了对我们的方法进行描述和优化，我们计划实现以下目标： 目标1：优化OPM光学传输和经皮/无线光遗传刺激 设备。 目标2：优化调制器和光学结构的功效，以确保长期安全 疼痛的治疗。 成功的研发有望通过一种高度特异的、 减轻疼痛的个人化方法，减少危险和增加奖励。这部小说 光遗传疗法可以应用于几种有潜力的慢性疼痛综合征 申请其他神经疾病。