CGRP, Amylin, Immunology, and Headache Medicine.

Abstract

Calcitonin gene-related peptide (CGRP) therapeutics introduce new excitement and possibly yet to be determined distressing discords in the field of Headache Medicine. Growth in knowledge of CGRP in the pathophysiology of migraine introduced CGRP antagonism to headache treatment. Potential adverse effects on the other circulatory and neurovascular diseases have been foremost concerns. Failures in development of gepants and growth in knowledge of monoclonal antibody therapeutics combined to deliver the anti-CGRP monoclonal antibodies (mAbs). CURRENT SITUATION AS OF JULY 2018: Erenumab, eptinezumab, fremanezumab, and galcanezumab are approved, submitted to, or preparing for submission at both the European Medicines Agency and the US Food and Drug Administration (FDA). This Headache Currents update emanates from a symposium on CGRP and immunology in Headache Medicine, and reviews both. Understanding CGRP in Headache Medicine requires information on aspects of the CGRP ligand, cell surface G protein receptor, CGRP receptor specifics, and antagonism by CGRP small and large molecules. Recent reports of CGRP's high affinity for amylin receptors dictate some attention to this family-related peptide. To better understand potential immunogenic risks and off-target toxicities of the anti-CGRP monoclonal antibodies, this review discusses immunology and CGRP and reviews IgG structure and function, monoclonal antibody production, ligand-antigen-antibody relationships, and clinical CGRP mAb specifics. Upon completion, the reader should better summarize CGRP antagonist fundamentals, recall antibody structure and function, restate therapeutic mAbs attributes, and appraise immunogenic risks.