Ion channel targets for treatment of neuropathic pain

治疗神经性疼痛的离子通道靶点

• 批准号: 6739208
• 负责人: TODD A VERDOORN
• 金额: $ 10万
• 依托单位: ALGOS THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739208
• 关键词: analgesics; antisense nucleic acid; biological signal transduction; calcium channel; drug discovery /isolation; hyperalgesia; immunocytochemistry; laboratory rat; messenger RNA; neuropathology; pain; perception; polymerase chain reaction; protein localization; spinal nerves; western blottings

DESCRIPTION (provided by applicant): Algos Therapeutics, Inc., a biopharmaceutical company, seeks funding for early drug discovery research designed to validate two proprietary ion channels as molecular targets for treatment of neuropathic pain. Neuropathic pain is initiated by nerve damage and appears to involve excessive electrical activity in sensory neurons and inappropriate inflammation of peripheral receptive fields. Patients with diabetes, cancer, arthritis, multiple sclerosis, and viral infections (herpes) are at risk for neuropathic pain. Few effective therapies for this type of chronic pain are now available. This Phase I SBIR proposal encompasses research that will determine where these targets are located both throughout the body and specifically in pain pathways. This will be done through measurment of mRNA encoding our targets and detection of the target proteins using immunocytochemistry and Western blot technology. The targets will be further validated using animal models of neuropathic pain. The normal function of the targets will be blocked by administration of antisense oligonucleotides to the intrathecal space. This treatment will reduce the amount of the targets expressed in the pain pathways and thereby reduce their normal function. Behavioral measures of allodynia and thermal hyperalgesia will be used to evaluate the analgesia generated by antisense treatment. Preliminary data suggests that our targets are involved in pain signaling and demonstrates our technical capabilities as well as the feasibility of our strategy. The goal of this Phase I project is to determine which of our two targets represents the most biologically important choke point of pain perception. The Phase II proposal will involve later stage drug discovery research such as assay development, lead seeking, and lead optimization. The immediate goal of this project is to produce a compound directed at our most attractive molecular target that is ready for human clinical testing. The long-term goal of our work is to develop an effective and safe treatment for neuropathic pain.

描述（由申请人提供）：Algos Therapeutics, Inc. 是一家生物制药公司，正在为早期药物发现研究寻求资金，该研究旨在验证两种专有离子通道作为治疗神经性疼痛的分子靶标。神经性疼痛由神经损伤引发，似乎涉及感觉神经元的过度电活动和外周感受野的不适当炎症。患有糖尿病、癌症、关节炎、多发性硬化症和病毒感染（疱疹）的患者面临神经性疼痛的风险。目前对于这种类型的慢性疼痛几乎没有有效的治疗方法。第一阶段 SBIR 提案涵盖的研究将确定这些目标在整个身体中的位置，特别是在疼痛通​​路中的位置。这将通过测量编码我们靶点的 mRNA 并使用免疫细胞化学和蛋白质印迹技术检测靶蛋白来完成。这些目标将使用神经性疼痛的动物模型进一步验证。将反义寡核苷酸施用到鞘内空间将阻断靶标的正常功能。这种治疗将减少疼痛通路中表达的靶标数量，从而降低其正常功能。异常性疼痛和热痛觉过敏的行为测量将用于评估反义治疗产生的镇痛作用。初步数据表明，我们的目标涉及疼痛信号传导，并证明了我们的技术能力以及我们策略的可行性。第一阶段项目的目标是确定我们的两个目标中哪一个代表了疼痛感知的最重要的生物学瓶颈。第二阶段提案将涉及后期药物发现研究，例如分析开发、先导化合物寻找和先导化合物优化。该项目的近期目标是生产一种针对我们最具吸引力的分子靶点的化合物，并为人类临床测试做好准备。我们工作的长期目标是开发一种有效且安全的神经病理性疼痛治疗方法。