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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.
AuthorsMarcelo E Bigal, Sarah Walter
JournalCNS drugs (CNS Drugs) Vol. 28 Issue 5 Pg. 389-99 (May 2014) ISSN: 1172-7047 [Print] New Zealand
PMID24638916 (Publication Type: Journal Article, Review)
Chemical References
  • Antibodies, Monoclonal
  • Receptors, Calcitonin Gene-Related Peptide
  • Calcitonin Gene-Related Peptide
Topics
  • Animals
  • Antibodies, Monoclonal (adverse effects, therapeutic use)
  • Calcitonin Gene-Related Peptide (metabolism)
  • Drug Discovery
  • Humans
  • Migraine Disorders (drug therapy, physiopathology)
  • Receptors, Calcitonin Gene-Related Peptide (antagonists & inhibitors)

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