Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov. The search term used was “cluster headache and calcitonin gene related peptide” and “primary headaches and calcitonin gene related peptide.”
Calcitonin gene-related peptide (CGRP) is a signaling neuropeptide released from activated trigeminal sensory afferents in headache and facial pain disorders. There are a handful of CGRP-targeted therapies currently in phase 3 studies for migraine acute treatment or prevention. Currently, 4 monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab).
Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration.