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，完全扰乱患者的生活，影响近3%，并且非常难以治疗。可以说，偏头痛研究的最高优先级是开发新药，但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。该提议试图最大化现有偏头痛模型的益处，增加体外和体内的通量和可靠性，以便可以进行标准化测试。我们将使用基于光学的多动物平台来增加皮质扩散性抑制（CSD）模型在体内的吞吐量和数据丰富性。我们将验证这个模型对我们以前的结果，以及那些有经验的CSD研究人员在另一个机构。我们还将使用硝酸甘油模型的偏头痛没有先兆，以补充CSD模型，这是最相关的偏头痛先兆。最后，我们将部署CSD的高通量脑切片模型，这是通过我们与合作者开发的新型微流体设备实现的。我们将用一系列已知在CSD和偏头痛中有活性（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测试来显着推进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.