Tools for migraine drug development

偏头痛药物开发工具

• 批准号: 8638730
• 负责人: Kevin Christopher Brennan
• 金额: $ 22.35万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638730
• 关键词: Address; Affect; American; Animal Model; Animals; Anticonvulsants; Auras; Biological Assay; Brain; Chronic; Classic Migraine; Common Migraine; Complement; Contracts; Convulsants; Data; Development; Devices; Disease; Drug Controls; Drug usage; Genetic; Genotype; Goals; Grant; Human; Image Analysis; In Vitro; Individual; Institution; Methods; Microfluidic Microchips; Microfluidics; Migraine; Modeling; Mus; Neurobiology; Neurosciences; Nitroglycerin; Optics; Pain; Pathway interactions; Pharmaceutical Preparations; Population; Preclinical Drug Evaluation; Predisposition; Prevention; Preventive; Protocols documentation; Research; Research Personnel; Slice; Spreading Cortical Depression; System; Techniques; Technology; Test Result; Testing; Thermal Hyperalgesias; Universities; Utah; Work; base; cost; drug development; drug efficacy; experience; in vivo; in vivo Model; insight; mechanical allodynia; medical specialties; new technology; novel; novel therapeutic intervention; optical imaging; programs; public health relevance; screening; sex; tool

DESCRIPTION (provided by applicant): Migraine affects 12% of the world population. Chronic migraine, which completely disrupts the lives of sufferers, affects close to 3%, and is extremely difficult to treat. Arguably the highest priority in migraine research is the development of new drugs, yet not a single drug has been developed specifically for the prevention of migraine. Fortunately, migraine models have made significant advances in recent years, and new systems neuroscience tools have opened up possibilities for further work. This proposal attempts to maximize the benefits of existing migraine models, increasing throughput and reliability both in vitro and in vivo, so that standardized testing can take place. We will use an optically-based multi-animal platform to increase the throughput and data-richness of the cortical spreading depression (CSD) model in vivo. We will validate this model against our prior results as well as those of an experienced CSD researcher at another institution. We will also use the nitroglycerin model of migraine without aura to complement the CSD model, which is most relevant to migraine with aura. Finally, we will deploy a high-throughput brain slice model of CSD, made possible by novel microfluidic devices we have developed with our collaborators. We will test the model with an array of compounds known to be active (and inactive) in CSD and migraine. Overall, our proposal should significantly advance efforts to develop new migraine treatments, by providing modular, immediately usable screening tests for migraine drugs.

描述（由申请人提供）：偏头痛影响世界人口的 12%。慢性偏头痛完全扰乱了患者的生活，影响了近 3% 的患者，而且极其难以治疗。可以说，偏头痛研究的首要任务是开发新药，但目前还没有一种药物专门用于预防偏头痛。幸运的是，偏头痛模型近年来取得了重大进展，新的系统神经科学工具为进一步的工作开辟了可能性。该提案试图最大限度地发挥现有偏头痛模型的优势，提高体外和体内的通量和可靠性，以便进行标准化测试。我们将使用基于光学的多动物平台来提高体内皮质扩散抑制（CSD）模型的吞吐量和数据丰富度。我们将根据我们之前的结果以及另一家机构经验丰富的 CSD 研究人员的结果来验证该模型。我们还将使用无先兆偏头痛的硝酸甘油模型来补充与有先兆偏头痛最相关的 CSD 模型。最后，我们将部署 CSD 的高通量脑切片模型，该模型是通过我们与合作者开发的新型微流体设备实现的。我们将使用一系列已知对 CSD 和偏头痛有效（和无效）的化合物来测试该模型。总体而言，我们的建议应通过提供模块化、立即可用的偏头痛药物筛选测试，显着推进开发新的偏头痛治疗方法的努力。