Recognizing the role of CGRP in migraine and its treatment

Karin Warfvinge | Dec 2019 | Migræne - FOKUS | Neurologi |

Karin Warfvinge
Klinisk Eksperimentel
Rigshospitalet Glostrup

An exciting group of medication uses a unique strategy to treat migraine, a medication which interferes with the signaling of a potent neuropeptide expressed in sensory nerves – calcitonin gene-related peptide (CGRP).  Inhibition of CGRP signaling has consistently shown positive effects in all clinical trials, from aborting acute attacks with CGRP receptor antagonists (gepants) to preventing attacks in chronic or frequent episodic migraine with monoclonal antibodies (mAbs) against CGRP or the CGRP receptor.  In 2018, the migraine specific drug (Aimovig®), a monoclonal antibody against the CGRP receptor, and two antibodies towards the CGRP molecule itself (AJOVY® and Emgality®) were approved by US FDA and EU EMA.1 Today, an estimation of 600.000 migraine patients worldwide are treated with either of these monoclonal antibodies.  CGRP was discovered 19822 and, in 1985, professor Lars Edvinsson was first to propose CGRP playing a role in migraine.3 Our research group was instrumental in discovering that CGRP is elevated in migraine headache4 and we have worked for over 30 years to help establish the role of CGRP in migraine pathophysiology.5  To understand how CGRP therapies affect migraine, it is important to define the role of CGRP in the trigeminovascular system, a key target for preventing migraine symptoms. The current theory behind the trigeminovascular system and migraine headache is as follows. The migraine attack is initiated in the central nervous system in the hypothalamus–thalamus–brainstem circuit that are referred to as “migraine generators”.6  During the headache phase, the trigeminal system/ganglion is activated and CGRP is released into the cranial circulation. In the trigeminal ganglion, 50 % of the neurons contain CGRP7,8 and there are no barriers to the peripheral circulation.  The afferent nerves from the trigeminal system/ganglion terminate behind the blood-brain barrier in the trigeminocervical complex and second-order neurons then project the pain signal through ascending pain pathways...