Scuteri Damiana, Adornetto Annagrazia, Rombolà Laura, Naturale Maria Diana, Morrone Luigi Antonio, Bagetta Giacinto, Tonin Paolo, Corasaniti Maria Tiziana
Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition, University of Calabria, Cosenza, Italy.
Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
Front Pharmacol. 2019 Apr 9;10:363. doi: 10.3389/fphar.2019.00363. eCollection 2019.
Migraine is a common neurologic disorder characterized by attacks consisting of unilateral, throbbing headache accompanied by photophobia, phonophobia, and nausea which remarkably reduces the patients' quality of life. Not migraine-specific non-steroidal anti-inflammatory drugs (NSAIDs) are effective in patients affected by mild episodic migraine whilst in moderate or severe episodic migraine and in chronic migraineurs triptans and preventative therapies are needed. Since these treatments are endowed with serious side effects and have limited effectiveness new pharmacological approaches have been investigated. The demonstrated pivotal role of calcitonin gene-related peptide (CGRP) has fostered the development of CGRP antagonists, unfortunately endowed with liver toxicity, and monoclonal antibodies (mAbs) toward circulating CGRP released during migraine attack or targeting its receptor. Currently, four mAbs, eptinezumab, fremanezumab, galcanezumab for CGRP and erenumab for CGRP canonical receptor, have been studied in clinical trials for episodic and chronic migraine. Apart from the proven effectiveness, these antibodies have resulted well tolerated and could improve the compliance of the patients due to their long half-lives allowing less frequent administrations. This study aims at investigating the still poorly clear pathogenesis of migraine and the potential role of anti-CGRP mAbs in the scenario of prophylaxis of migraine.
偏头痛是一种常见的神经系统疾病，其发作特征为单侧搏动性头痛，并伴有畏光、畏声和恶心，这显著降低了患者的生活质量。非偏头痛特异性非甾体抗炎药（NSAIDs）对轻度发作性偏头痛患者有效，而在中度或重度发作性偏头痛以及慢性偏头痛患者中，则需要使用曲坦类药物和预防性治疗。由于这些治疗存在严重的副作用且效果有限，因此人们一直在研究新的药理学方法。降钙素基因相关肽（CGRP）已被证明具有关键作用，这推动了CGRP拮抗剂的研发，遗憾的是，这些拮抗剂具有肝毒性，以及针对偏头痛发作期间释放的循环CGRP或其受体的单克隆抗体（mAb）。目前，四种单克隆抗体，即用于CGRP的依普奈珠单抗、夫雷奈珠单抗、加卡奈珠单抗以及用于CGRP经典受体的erenumab，已在发作性和慢性偏头痛的临床试验中进行了研究。除了已证实的有效性外，这些抗体耐受性良好，并且由于其半衰期长，给药频率较低，因此可以提高患者的依从性。本研究旨在探讨偏头痛发病机制仍不明确的情况以及抗CGRP单克隆抗体在偏头痛预防中的潜在作用。
