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CGRP, Amylin, Immunology, and Headache Medicine.
Headache. 2019 01; 59(1):131-150.H

Abstract

BACKGROUND

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).

METHODS

This Headache Currents update emanates from a symposium on CGRP and immunology in Headache Medicine, and reviews both.

RESULTS AND CONCLUSION

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30390312

Citation

Taylor, Frederick R.. "CGRP, Amylin, Immunology, and Headache Medicine." Headache, vol. 59, no. 1, 2019, pp. 131-150.
Taylor FR. CGRP, Amylin, Immunology, and Headache Medicine. Headache. 2019;59(1):131-150.
Taylor, F. R. (2019). CGRP, Amylin, Immunology, and Headache Medicine. Headache, 59(1), 131-150. https://doi.org/10.1111/head.13432
Taylor FR. CGRP, Amylin, Immunology, and Headache Medicine. Headache. 2019;59(1):131-150. PubMed PMID: 30390312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CGRP, Amylin, Immunology, and Headache Medicine. A1 - Taylor,Frederick R, Y1 - 2018/11/03/ PY - 2018/09/24/accepted PY - 2018/11/6/pubmed PY - 2020/5/28/medline PY - 2018/11/4/entrez KW - CGRP antagonism KW - amylin KW - calcitonin gene-related peptide KW - cell surface G protein receptors KW - hybridoma KW - monoclonal antibodies SP - 131 EP - 150 JF - Headache JO - Headache VL - 59 IS - 1 N2 - BACKGROUND: 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). METHODS: This Headache Currents update emanates from a symposium on CGRP and immunology in Headache Medicine, and reviews both. RESULTS AND CONCLUSION: 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. SN - 1526-4610 UR - https://www.unboundmedicine.com/medline/citation/30390312/CGRP_Amylin_Immunology_and_Headache_Medicine_ L2 - https://doi.org/10.1111/head.13432 DB - PRIME DP - Unbound Medicine ER -