The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene-related peptide (CGRP) within the context of the trigeminovascular system.
Recently, the fully human monoclonal antibody erenumab (AMG 334), which targets the canonical calcitonin gene-related peptide receptor, showed significant prophylactic efficacy and favourable safety in phase II and III clinical trials for episodic and chronic migraine and is now approved for migraine prevention in several countries.
Specificity, long half-life, efficacy, tolerability, and ease of use make monoclonal antibodies targeting the calcitonin gene-related peptide or its receptor an appealing treatment option for migraine prevention.
<b>Introduction</b>: The recent approval of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway introduced the first preventive treatments for migraine that were specifically designed to target the underlying pathophysiology of the disease.
<b>Areas covered</b>: This paper briefly discusses the calcitonin family of neurotransmitters and resultant activation pathways and in-depth the chemical properties, pharmacodynamics, pharmacokinetics, clinical efficacy and safety of Fremanezumab for the prophylactic treatment of migraine.
Fremanezumab is a fully humanized IgG<sub>2</sub> Δa/κ monoclonal antibody specific for calcitonin gene-related peptide developed and approved for the preventive treatment of migraine in adults.
In this respect, calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology and, more recently, the functional interactions between ovarian steroid hormones, CGRP and the trigeminovascular system have been recognized and studied in more detail.
Fremanezumab is a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, a neuropeptide involved in the pathophysiology of migraine.
The evolution of CGRPmigraine science gave impetus to the development of peripherally acting drugs that could modulate CGRP chronically to prevent frequent episodic and chronic migraine.
This review focuses on describing Calcitonin Gene Related Peptide Monoclonal Antibodies (CGRP-mABs) efficacy on improving the quality of life (QoL) and decreasing the disability and impact of migraine measured with patient related outcomes (PROs), on patients who participated in clinical trials with erenumab, fremanezumab, galcanezumab and eptinezumab.
An important novel finding is that both sildenafil and calcitonin gene-related peptide dilate intradural arteries, supporting the notion that all known pharmacological migraine triggers dilate cephalic vessels.
In conclusion, the progresses in migraine management have been reached with the development of emerging agonists of 5-HT receptors and novel antagonists of CGRP receptors.
We observed a close relationship between the CGRP containing C-fibers and the Aδ-fibers containing the CGRP-receptor elements, suggesting a point of axon-axon interaction for the released CGRP and a site of action for gepants and the novel mAbs to alleviate migraine.
Moreover, the unexpected rapidity of onset observed for ALD405 supports i) a probable site of action outside the blood-brain barrier, and ii) a potential clinical utility of specific monoclonal calcitonin gene-related peptide antibodies in the abortive treatment of migraine.
One of the prevailing mechanisms is the activation of the trigeminovascular system, and calcitonin gene-related peptide (CGRP) is an important therapeutic target for migraine in this system.