Emerging Concepts in Migraine and Targeting PACAP: Dolores Santamaria, MD


The director of the Headache Center at Allegheny Health Network provided an overview of clinically relevant approaches to treat migraine at its core pathology. [WATCH TIME: 2 minutes]

WATCH TIME: 2 minutes

"This pathway is in the same kind of category as calcitonin gene-related peptide pathways. This is all pain modulation that can definitely trigger that attack. So blocking or preventing that signaling pathway can help in the further evolution of different treatments."

In 2018, the approach to treating migraine was drastically changed, as the FDA approved erenumab (Aimovig; Amgen), the first ever calcitonin gene-related peptide (CGRP) inhibitor. These agents block the effect of CGRP, a small protein that is highly prevalent in the sensory nerves that supply the head and neck. CGRP is also involved in pain transmission and levels increase during a migraine attack. While these therapies have brought considerable relief to the clinical community, there are a proportion of patients with migraine who do not respond to these medications.

Considered the most common cause of neurological disability worldwide, there is a constant need for new approaches to treat the condition. Since its first publication in Brain as a migraine inducing substance in 2009, there has been a steady increase in research focused on targeting enkephalins and pituitary adenylate cyclase-activating polypeptide (PACAP), a relatively new pathway. PACAP exists in 2 biologically active forms, PACAP-27 and PACAP-38. PACAP-38, the predominant form, has shown a remarkable degree of evolutionary conservation in preclinical studies.1

To learn more about the emerging concepts in the migraine field, NeurologyLive® sat down with Dolores Santamaria, MD, director of the Headache Center at Allegheny Health Network. Santamaria, who specializes in treating patients with chronic migraine, provided an overview on PACAP, how it differs from CGRP, and the conversations surrounding it.

Rubio-Beltrán E, Correnti E, Deen M, et al. PACAP38 and PAC1 receptor blockade: a new target for headache? J Headache Pain. 2018;19(1):64. doi:10.1186/s10194-018-0893-8
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