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： 疾病和损伤最常见的明显症状是疼痛。它可以警告危险或 需要治疗一个问题，但是，当它变成慢性时，它可能会变得虚弱。慢性的 据估计，疼痛影响着全球多达三分之一的成年人口（Majeed et al., 2018）。 疼痛治疗的并发症继续导致成瘾和伤害（包括死亡）。 治疗慢性疼痛（尤其是顽固性疼痛）的替代方法对于 解决慢性疼痛本身并减轻长期服用药物的危害 目前的治疗方法。从持续的阿片类药物危机和巨大的成本中可以看出 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 可能很可怕。这会导致生活质量和生产力下降。光遗传学提供了 高度特异性和可定制的细胞活动控制的可能性，打开途径 通过细胞特异性降低风险的治疗方法，同时还允许个性化治疗。 目前，最常见的视蛋白需要过多的能量才能激活，或者无法激活。 对可能损伤组织的光波长敏感，从而限制了它们在医疗中的应用 治疗。为了解决这些限制，我们开发了一种独特的敏感视蛋白和 刺激装置可以提供视蛋白的有针对性和定制的激活。多- 特征视蛋白 (MCO) 可以传递到参与感觉和处理的神经元 疼痛并根据需要进行刺激，以尽量减少疼痛感。初步研究有 建立了疼痛光遗传学调节的基线参数，我们继续 研究确定了这种疼痛管理方法的价值和安全性。为进一步 通过表征和优化我们的方法，我们计划实现以下目标： 目标 1：优化 OPM 光学传输和透皮/无线光遗传学刺激 设备。 目标 2：优化调制器和视蛋白构建体的功效，实现长期安全 治疗疼痛。 成功的开发有望通过高度具体的、 个性化的缓解疼痛方法，减少危险并增加回报。这部小说 光遗传学治疗可应用于多种慢性疼痛综合征，具有潜在的应用前景 其他神经系统疾病的应用。