Migraine Research Uncovers New Drug Targets and Treatment Pathways

Recent scientific studies have led to a deeper understanding of migraine mechanisms, prompting renewed investigation into drug targets that were previously set aside decades ago.

Current research has identified several biological pathways involved in migraine, including those related to calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP). These findings have influenced the development of new therapies and revived interest in older targets for potential treatments.

CGRP receptor antagonists have become a central focus in migraine therapy over the past several years. The FDA approved erenumab, marketed as Aimovig, in May 2018 as the first preventive monoclonal antibody targeting CGRP for migraine prevention. Zavegepant, another CGRP receptor antagonist, became available in the United States in March 2023 as a nasal spray for acute migraine attacks.

In addition to CGRP-based treatments, a June 2025 study reported that liraglutide, a diabetes medication classified as a GLP-1 receptor agonist, reduced the number of monthly migraine days by more than half in obese patients with chronic migraine. Researchers suggested this effect may be linked to a reduction in brain fluid pressure.

What the numbers show

• Erenumab was approved by the FDA for migraine prevention in May 2018
• Zavegepant nasal spray received US approval in March 2023
• Liraglutide reduced monthly migraine days by over 50% in a June 2025 study

Further research has explored how stress may contribute to migraines. One study found that stress-induced migraines could result from PACAP-38 binding to MrgprB2 receptors on mast cells, which triggers inflammation and sensitizes the trigeminal nerve. This mechanism suggests additional therapeutic options beyond current treatments.

Investigations using animal models have also identified new molecular pathways. A mouse study showed that cortical spreading depression, a process linked to migraine, alters the flow of cerebrospinal fluid to the trigeminal ganglia. This fluid can carry proteins such as CGRP, indicating that other molecules transported in this way may be relevant for future migraine therapies.

Research into PACAP and its receptors as migraine drug targets has produced mixed results. For example, Alder’s ALD1910, which targets PACAP, entered phase I clinical trials in October 2019. In contrast, Amgen’s AMG-301, which targets the PAC1 receptor, did not meet its goals in a phase II trial.

These developments reflect a growing body of evidence that multiple molecular pathways are involved in migraine, leading to a broader range of potential therapeutic strategies. Ongoing studies continue to assess how targeting different biological mechanisms may improve migraine management for various patient groups.

* This article is based on publicly available information at the time of writing.