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Related Experiment Video

Updated: Sep 20, 2025

3D-Neuronavigation In Vivo Through a Patient's Brain During a Spontaneous Migraine Headache

3D-Neuronavigation In Vivo Through a Patient's Brain During a Spontaneous Migraine Headache

Published on: June 2, 2014

PACAP and migraine.

Hans Christoph Diener¹

¹Department of Neuroepidemiology, Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), Faculty of Medicine, University Duisburg-Essen, Essen 45147, Germany.

Brain : a Journal of Neurology

|May 30, 2025

Summary

Pituitary adenylate cyclase-activating polypeptide (PACAP) is implicated in migraine pathophysiology. A PACAP-targeting antibody (Lu AG09222) showed promise in reducing monthly migraine days in a proof-of-concept study.

Keywords:

calcitonin gene related peptide (CGRP)migraine migraine prevention pituitary adenylate cyclase-activating polypeptide (PACAP)

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Area of Science:

Neuroscience
Pharmacology

Background:

Neuropeptides like pituitary adenylate cyclase-activating polypeptide (PACAP) are involved in migraine pathophysiology.
PACAP administration can trigger migraine attacks in susceptible individuals.
Previous attempts targeting the PACAP receptor with a monoclonal antibody did not demonstrate efficacy.

Purpose of the Study:

To evaluate the efficacy of a monoclonal antibody targeting PACAP (Lu AG09222) for migraine prevention.
To assess the impact of Lu AG09222 on monthly migraine days and other relevant endpoints.

Main Methods:

A small, short, proof-of-concept study was conducted.
The study compared Lu AG09222 to a placebo.
The primary endpoint assessed was the reduction in monthly migraine days.

Main Results:

Lu AG09222 demonstrated efficacy in reducing monthly migraine days compared to placebo.
The antibody did not meet the endpoint for a 50% reduction in migraine days.

Conclusions:

PACAP is a relevant target for migraine prevention.
Further investigation with Lu AG09222 is warranted, as suggested by the ongoing PROCEED study.
The PROCEED study will further evaluate dose-finding for Lu AG09222 in migraine prevention.