CGRP/CGRP Receptor Antibodies: Potential Adverse Effects Due to Blockade of Neovascularization?

Masataka Majima; Yoshiya Ito; Kanako Hosono; Hideki Amano

doi:10.1016/j.tips.2018.11.003

CGRP/CGRP Receptor Antibodies: Potential Adverse Effects Due to Blockade of Neovascularization?

Trends Pharmacol Sci. 2019 Jan;40(1):11-21. doi: 10.1016/j.tips.2018.11.003. Epub 2018 Nov 28.

Authors

Masataka Majima¹, Yoshiya Ito², Kanako Hosono², Hideki Amano²

Affiliations

¹ Department of Pharmacology, Kitasato University School of Medicine and Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan. Electronic address: mmajima@med.kitasato-u.ac.jp.
² Department of Pharmacology, Kitasato University School of Medicine and Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan.

PMID: 30502971
DOI: 10.1016/j.tips.2018.11.003

Abstract

Migraine is a severe neurological disorder in which calcitonin gene-related peptide (CGRP) is a key molecule in pathophysiology. Neuronal system-derived CGRP enhances neovascularization in several important pathological conditions and sends a cue to the vascular system. In 2018, the FDA approved erenumab and fremanezumab, antibodies against CGRP receptor and CGRP, as the first new class of drugs for migraine. Treatment of migraine with these antibodies requires great care because neovascularization-related adverse effects may be induced in some patients. Here, we focus on enhancement of neovascularization by CGRP and discuss possible adverse effects resulting from blocking neovascularization. We also suggest that CGRP antibodies may also be used as novel antitumor agents by suppressing tumor-associated angiogenesis.

Keywords: angiogenesis; antibody; calcitonin gene-related peptide; lymphangiogenesis; migraine; neuronal system.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Angiogenesis Inhibitors / administration & dosage
Angiogenesis Inhibitors / adverse effects
Angiogenesis Inhibitors / pharmacology
Animals
Antibodies, Monoclonal / administration & dosage*
Antibodies, Monoclonal / adverse effects
Antibodies, Monoclonal / pharmacology
Antibodies, Monoclonal, Humanized / administration & dosage
Antibodies, Monoclonal, Humanized / adverse effects
Antibodies, Monoclonal, Humanized / pharmacology
Calcitonin Gene-Related Peptide / immunology*
Calcitonin Gene-Related Peptide / metabolism
Humans
Migraine Disorders / drug therapy
Migraine Disorders / immunology
Neoplasms / blood supply
Neoplasms / drug therapy
Neovascularization, Pathologic / drug therapy
Neovascularization, Pathologic / pathology
Receptors, Calcitonin Gene-Related Peptide / immunology*
Receptors, Calcitonin Gene-Related Peptide / metabolism

Substances

Angiogenesis Inhibitors
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Receptors, Calcitonin Gene-Related Peptide
fremanezumab
erenumab
Calcitonin Gene-Related Peptide