Tools for migraine drug development

描述(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%，而且极难治疗。可以说，偏头痛研究的首要任务是开发新药，但还没有专门为预防偏头痛开发的单一药物。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研究打开了可能性。这项建议试图最大限度地利用现有偏头痛模型的好处，增加体外和体内的吞吐量和可靠性，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层扩散性抑制(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家机构有经验的CSD研究员的结果来验证这个模型。我们还将使用无先兆偏头痛的硝酸甘油模型来补充CSD模型，CSD模型与有先兆的偏头痛最相关。最后，我们将部署CSD的高通量脑片模型，这是由我们与合作伙伴开发的新型微流控设备实现的。我们将用一系列已知对慢性阻塞性肺病和偏头痛有效(和无效)的化合物来测试该模型。总体而言，通过提供模块化的、立即可用的偏头痛药物筛查测试，我们的提案应该会显著推动开发新的偏头痛治疗方法的努力。

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.