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.
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Authors | Marcelo E Bigal, Sarah Walter |
Journal | CNS drugs
(CNS Drugs)
Vol. 28
Issue 5
Pg. 389-99
(May 2014)
ISSN: 1179-1934 [Electronic] New Zealand |
PMID | 24638916
(Publication Type: Journal Article, Review)
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Chemical References |
- Antibodies, Monoclonal
- Calcitonin Gene-Related Peptide Receptor Antagonists
- Calcitonin Gene-Related Peptide
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Topics |
- Animals
- Antibodies, Monoclonal
(adverse effects, therapeutic use)
- Calcitonin Gene-Related Peptide
(metabolism)
- Calcitonin Gene-Related Peptide Receptor Antagonists
- Drug Discovery
- Humans
- Migraine Disorders
(drug therapy, physiopathology)
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