Department of Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.
VA Center for the Prevention and Treatment of Visual Loss, VA Medical Center, Iowa City, IA, USA.
Expert Opin Ther Targets. 2020 Feb;24(2):91-100. doi: 10.1080/14728222.2020.1724285. Epub 2020 Feb 13.
: The neuropeptide calcitonin gene-related peptide (CGRP) is recognized as a critical player in migraine pathophysiology. Excitement has grown regarding CGRP because of the development and clinical testing of drugs targeting CGRP or its receptor. While these drugs alleviate migraine symptoms in half of the patients, the remaining unresponsive half of this population creates an impetus to address unanswered questions that exist in this field.: We describe the role of CGRP in migraine pathophysiology and CGRP-targeted therapeutics currently under development and in use. We also discuss how a second CGRP receptor may provide a new therapeutic target.: CGRP-targeting drugs have shown a remarkable safety profile. We speculate that this may reflect the redundancy of peptides within the CGRP family and a second CGRP receptor that may compensate for reduced CGRP activity. Furthermore, we propose that an inherent safety feature of peptide-blocking antibodies is attributed to the fundamental nature of peptide release, which occurs as a large bolus in short bursts of volume transmission. These facts support the development of more refined CGRP therapeutic drugs, as well as drugs that target other neuropeptides. We believe that the future of migraine research is bright with exciting advances on the horizon.
降钙素基因相关肽（CGRP）是偏头痛病理生理学中的关键角色。由于靶向 CGRP 或其受体的药物的开发和临床测试，人们对 CGRP 的兴趣日益浓厚。虽然这些药物能使一半的偏头痛患者的症状得到缓解，但另一半没有反应的患者促使人们去解决该领域存在的未解决问题。我们描述了 CGRP 在偏头痛病理生理学中的作用以及目前正在开发和使用的 CGRP 靶向治疗药物。我们还讨论了第二个 CGRP 受体如何提供一个新的治疗靶点。CGRP 靶向药物具有显著的安全性。我们推测这可能反映了 CGRP 家族内肽的冗余性和第二个 CGRP 受体可能会代偿减少的 CGRP 活性。此外，我们提出肽阻断抗体的固有安全性特征归因于肽释放的基本性质，即作为体积传递的短爆发中大量的脉冲式释放。这些事实支持开发更精细的 CGRP 治疗药物，以及针对其他神经肽的药物。我们相信，偏头痛研究的未来是光明的，前景令人兴奋。
