title: Monoclonal antibodies for migraine: preventing calcitonin gene-related peptide activity.
abstract: Calcitonin gene-related peptide (CGRP) is a well-studied neuropeptide of relevance for migraine pathophysiology. Jugular levels of CGRP are increased during migraine attacks, and intravenous CGRP administration induces migraine-like headache in most individuals with migraine. Several CGRP receptor antagonists (CGRP-RAs) were shown to be effective for the acute treatment of migraine, validating the target for the treatment of migraine. However, for a number of reasons, including issues of liver toxicity with chronic use, the development of CGRP-RAs has yet to produce a viable clinical therapeutic. Development of monoclonal antibodies (mAbs) targeting the CGRP pathway is an alternative approach that should avoid many of the issues seen with CGRP-RAs. The exquisite target specificity, prolonged half-lives, and reduced potential for hepatotoxicity and drug-drug interactions make mAbs suitable for the preventive treatment of migraine headaches. This manuscript provides an overview of the role of CGRP in the pathophysiology of migraine, followed by a review of the clinical development of CGRP-RAs. Some basic concepts on antibodies are then discussed along with the publicly disclosed information on the development of mAbs targeting the CGRP pathway.
authors.affiliation: Labrys Biologics Inc, 1810 Gateway Drive, Suite 230, San Mateo, CA, USA, mbigal@labrysbiologics.com.
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Bigal
authors.forename: Sarah
authors.initials: S
authors.lastname: Walter
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D055808:Drug Discovery; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000911:Antibodies, Monoclonal; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide