Human migraine models

Members

Messoud Ashina, Sohail Asghar, Jakob Møller Hansen, Henrik Schytz, Troels Wienecke, Anders Hougaard, Faisal Amin, Jes Olesen & Maria Antonova.

Background
Fast tracking of new drugs for migraine have faced the major challenge of poorlypredictive preclinical models. Indeed, novel, migraine-specific preventive drugs have not been developed in decades. Furthermore, the acute therapy armamentarium remains suboptimal, with no new chemical entities since the triptans. On the other hand, human experimental studies are surfacing as a powerful tool in targeted migraine therapy. To this end, human studies have identified three novel targets: inhibitors of cortical spreading depression, antagonists of calcitonin gene-related receptors, and chemicals that prevent the production of nitric oxide. Two of these novel mechanisms are in phase 3 clinical development and one is in phase 2. These encouraging observations, which are based on 20 years of research in human models, have led us to develop a research paradigm for the identification of novel migraine drug targets, which combines human provocation studies and preclinical models.

Current projects

• Role of prostaglandins in migraine pathophysiology: Effect of EP receptor antagonist in PGE2 model of headache
• PGF2lalfa model of headache
• Activation of trigeminal pain pathways during different sequences of CGRP induced migraine attack: fMRI study
• Changes in diameter of extra- and intracranial vessels during CGRP induced migraine attack: MRA study
• Changes in diameter of extra- and intracranial vessels during PACAP induced headache before and after sumatriptan administration: MRA study
• Intrinsic brain connectivity during PACAP induced headache: fMRI study

Collaboration
Henrik Larsson and Adam Espe Hansen (Department of Clinical Physiology); Vibeke Andre Larsen (Department of Radiology); David Borsook and Lino Becerra, PAIN Group, Mclean Hospital, Harvard University Boston USA; David A Boas, Optical Imaging Core & Lab at Martinos Centre Department of Radiology, Boston USA; Professor van der Geest, Leiden University Medical Centre, Holland.