Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Expert Opin Emerg Drugs. 2024 Mar;29(1):57-64. doi: 10.1080/14728214.2024.2317778. Epub 2024 Feb 12.
The pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) has emerged as a key mediator of migraine pathogenesis. PACAP-38 and its receptors are predominantly distributed in arteries, sensory and parasympathetic neurons of the trigeminovascular system. Phase 2 trials have tested human monoclonal antibodies designed to bind and inhibit PACAP-38 and the pituitary adenylate cyclase-activating polypeptide type I (PAC) receptor for migraine prevention.
This review focuses on the significance of the PACAP-38 pathway as a target in migraine prevention. English peer-reviewed articles were searched in PubMed, Scopus and ClinicalTrials.gov electronic databases.
A PAC receptor monoclonal antibody was not effective for preventing migraine in a proof-of-concept trial, paving the way for alternative strategies to be considered. Lu AG09222 is a humanized monoclonal antibody targeting PACAP-38 that was effective in preventing physiological responses of PACAP38 and reducing monthly migraine days in individuals with migraine. Further studies are necessary to elucidate the clinical utility, long-term safety and cost-effectiveness of therapies targeting the PACAP pathway.
垂体腺苷酸环化酶激活肽-38（PACAP-38）已成为偏头痛发病机制的关键介质。PACAP-38 及其受体主要分布在动脉、三叉神经系统的感觉和副交感神经元中。第二期临床试验已经测试了旨在结合和抑制 PACAP-38 和垂体腺苷酸环化酶激活肽 I 型（PAC）受体的人单克隆抗体，以预防偏头痛。
这篇综述重点介绍了 PACAP-38 途径作为偏头痛预防靶点的意义。在 PubMed、Scopus 和 ClinicalTrials.gov 电子数据库中搜索了英文同行评审文章。
在一项概念验证试验中，PAC 受体单克隆抗体预防偏头痛无效，为考虑替代策略铺平了道路。Lu AG09222 是一种针对 PACAP-38 的人源化单克隆抗体，可有效预防 PACAP38 的生理反应，并减少偏头痛患者每月偏头痛天数。需要进一步研究阐明针对 PACAP 途径的治疗方法的临床实用性、长期安全性和成本效益。
