Calcitonin Gene-Related Peptide (CGRP) is now firmly established in migraine pathophysiology. A number of lines of evidence support this:
- CGRP levels (both peripherally and centrally) increase during a severe migraine attack
- Elevated CGRP levels during a migraine attack are normalised with effective triptan treatment
- Intravenous infusion of CGRP can induce migraine-like attacks in patients with a history of migraine
- Administration of CGRP receptor antagonists has been shown to abort an attack
These findings have driven the development of new agents specifically targeting CGRP or its receptor. The first of these, the CGRP receptor antagonists or ‘gepants’, provided proof of concept but were subsequently terminated mainly due to safety concerns. Development is continuing for some of these agents in acute migraine.
Advances in monoclonal antibody technology have allowed the development of monoclonal antibodies to either CGRP or its receptor. Phase 3 trials are ongoing with some results already reported.