PACAP as a future target for anti-migraine medication

Messoud Ashina, MD, PhD, University of Copenhagen, Copenhagen, Denmark, describes the potential of targeting pituitary adenylate-cyclase-activating polypeptide (PACAP) for anti-migraine therapy. PACAP is a widely distributed neural peptide with various biological functions, including expression in the trigeminovascular system, long known to be involved in migraine pathophysiology. To delineate the function of PACAP in migraines, early studies performed intravenous infusion of PACAP, which resulted in 60% of patients reporting an increase in migraine attacks, highlighting PACAP as a migraine provoking agent. Additionally, Prof. Ashina’s lab showed that these PACAP-induced migraines were prevented when sumatriptan was administered early enough. PACAP acts on some receptors that have been suggested to be possible targets, but the first proof-of-concept study failed to show efficacy of monoclonal antibodies against one of these receptors. Nonetheless, PACAP is a promising target and Prof. Ashina notes that two ongoing trials are working on PACAP-directed monoclonal antibodies, targeting the migraine-inducing ligand itself. This interview took place at the European Academy of Neurology (EAN) 2022 Congress in Vienna, Austria.