Tools for migraine drug development

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，而且极难治疗。可以说，偏头痛研究中最优先考虑的是开发新药，但目前还没有一种专门用于预防偏头痛的药物。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。该建议试图最大化现有偏头痛模型的好处，增加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增加体内皮质扩张性抑制（CSD）模型的吞吐量和数据丰富性。我们将根据我们之前的结果以及另一所机构经验丰富的CSD研究人员的结果验证该模型。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，这是由我们与合作者开发的新型微流体装置实现的。我们将用一系列已知对CSD和偏头痛有活性（和无活性）的化合物来测试该模型。总的来说，我们的建议应该通过提供模块化的、立即可用的偏头痛药物筛选试验，显著地推进开发新的偏头痛治疗方法。

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.