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Headache. 2018 Nov;58 Suppl 3:230-237. doi: 10.1111/head.13409. Epub 2018 Sep 5.

Antigens and Antibodies in Disease With Specifics About CGRP Immunology.

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Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.


Growth in knowledge about calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine brought CGRP antagonism to headache medicine. Failures in development of small molecule CGRP receptor antagonists and increasing knowledge and use of monoclonal antibodies (mAbs) in medicine led to the breakthrough development of large molecule anti-CGRP mAbs: eptinezumab, erenumab, fremanezumab, and galcanezumab. This specifics about CGRP immunology aims to outline: (1) knowledge needed for CGRP antagonism and (2) developmental issues of specific CGRP antagonists for provider use. This clinically oriented review documents IgG structure and function; state of the art of monoclonal IgG production and ligand-antigen-antibodies in migraine therapeutics contributing to immunogenic risks and off-target toxicities. Specifics to CGRP ligand, receptor, antagonism, and molecules, small and large, complete this review. Completion will facilitate assessment of the similarities, differences, and application of the forthcoming anti-CGRP receptor and ligand antagonists for patients.


CGRP antagonism; anti-CGRP monoclonal antibodies; cell surface G protein receptors; hybridoma; immunoglobulin gamma


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