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Monoclonal Antibodies for Migraine: Preventing Calcitonin Gene-Related Peptide Activity

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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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Disclosure

The authors are full time employees of Labrys Biologics, a company developing an mAb against CGRP (LBR-101).

No funding was received for writing this article. The review represents the authors’ own work and no medical writers were involved in its planning or execution.

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    Marcelo E. Bigal & Sarah Walter

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Correspondence to Marcelo E. Bigal.

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Bigal, M.E., Walter, S. Monoclonal Antibodies for Migraine: Preventing Calcitonin Gene-Related Peptide Activity. CNS Drugs 28, 389–399 (2014). https://doi.org/10.1007/s40263-014-0156-4

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