Targeting the PACAP-38 pathway is an emerging therapeutic strategy for migraine prevention
Research output: Contribution to journal › Review › Research › peer-review
Introduction: 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 (PAC1) receptor for migraine prevention. Areas covered: 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. Expert opinion: A PAC1 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.
Original language | English |
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Journal | Expert Opinion on Emerging Drugs |
Volume | 29 |
Issue number | 1 |
Pages (from-to) | 57-64 |
Number of pages | 8 |
ISSN | 1472-8214 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:
© 2024 Informa UK Limited, trading as Taylor & Francis Group.
- CGRP, headache, medication overuse headache, monoclonal antibodies, pain, VIP
Research areas
ID: 390186761