Targeting the PACAP-38 pathway is an emerging therapeutic strategy for migraine prevention

Lanfranco Pellesi*, Messoud Ashina, Paolo Martelletti

*Corresponding author af dette arbejde
1 Citationer (Scopus)


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 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.

TidsskriftExpert Opinion on Emerging Drugs
Udgave nummer1
Sider (fra-til)57-64
Antal sider8
StatusUdgivet - mar. 2024


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