Promise in PACAP Pathway for Treating Migraine: Jessica Ailani, MD


The director of the MedStar Georgetown Headache Center provided insight on the excitement behind PACAP, how it may offer an alternate way of treating migraine, and where research behind it currently stands. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"It’s interesting because we’ve been so focused on talking about CGRP, what we haven’t talked about are all our failures. CGRP is the one that kind of made it through the hoops, but there are actually many peptides that have been looked at in the trigger of migraine and involved in the pathophysiology."

Soon after calcitonin gene-related peptide (CGRP) was discovered in 1983, it was linked to the trigeminovascular system with implications for migraine. Early studies of the calcitonin gene revealed that alternative splicing occurred in neural tissue, resulting in the expression of a second peptide named calcitonin gene-related peptide. Decades later, significant advances in drug development led to the introduction of GCRP-targeting treatments, which in clinical trials were all found to be effective with minor adverse effects.

Despite these effective agents, some patients remain drug-resistant, with difficulties finding treatments that resolve their migraineous status. In recent years, pituitary adenylate cyclase-activating polypeptide (PACAP) has emerged as a neuropeptide implicated in the pathophysiology of migraine and represents a novel target. Research into this pathway has steadily grown, with industry leaders starting to take interest.

Migraine expert Jessica Ailani, MD, notes that it’s been encouraging to see those in the field continue to take interest in PACAP despite some early trial failures. Ailani, director of the MedStar Georgetown Headache Center, recently sat down with NeurologyLive® at the 2023 International Congress on the Future of Neurology (IFN), held in Jersey City, New Jersey, from September 22-23, to discuss where research stands on PACAP, and the remaining questions that still need answering. She spoke on the mechanisms behind PACAP, its links with migraine, and the next steps in research.

Click here for more coverage of IFN 2023.

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