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CNS Drugs. 2014 May;28(5):389-99. doi: 10.1007/s40263-014-0156-4.

Monoclonal antibodies for migraine: preventing calcitonin gene-related peptide activity.

Author information

1
Labrys Biologics Inc, 1810 Gateway Drive, Suite 230, San Mateo, CA, USA, mbigal@labrysbiologics.com.

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.

PMID:
24638916
DOI:
10.1007/s40263-014-0156-4
[Indexed for MEDLINE]

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