Journal article
CGRP-Based Migraine Therapeutics: How Might They Work, Why So Safe, and What Next?
ACS pharmacology & translational science, Vol.2(1), pp.2-8
02/08/2019
DOI: 10.1021/acsptsci.8b00036
PMCID: PMC6761833
PMID: 31559394
Abstract
Migraine is a debilitating neurological condition that involves the neuropeptide calcitonin gene-related peptide (CGRP). An exciting development is the recent FDA approval of the first in an emerging class of CGRP-targeted drugs designed to prevent migraine. Yet despite this efficacy, there are some fundamental unanswered questions, such as where and how CGRP works in migraine. Preclinical data suggest that CGRP acts via both peripheral and central mechanisms. The relevance of peripheral sites is highlighted by the clinical efficacy of CGRP-blocking antibodies, even though they do not appreciably cross the blood-brain barrier. The most likely sites of action are within the dura and trigeminal ganglia. Furthermore, it would be foolish to ignore perivascular actions in the dura since CGRP is the most potent vasodilatory peptide. Ultimately, the consequence of blocking CGRP or its receptor is reduced peripheral neural sensitization. Underlying their efficacy is the question of why the antibodies have such an excellent safety profile so far. This may be due to the presence of a second CGRP receptor and vesicular release of a large bolus of peptides. Finally, despite the promise of these drugs, there are unmet gaps because they do not work for all patients; so what next? We can expect advances on several fronts, including CGRP receptor structures that may help the development of centrally acting antagonists, combinatorial treatments that integrate other therapies, and development of drugs that target other neuropeptides. This is truly an exciting time for CGRP and the migraine field with many more discoveries on the horizon.
Details
- Title: Subtitle
- CGRP-Based Migraine Therapeutics: How Might They Work, Why So Safe, and What Next?
- Creators
- Andrew F Russo - Center for the Prevention and Treatment of Visual Loss
- Resource Type
- Journal article
- Publication Details
- ACS pharmacology & translational science, Vol.2(1), pp.2-8
- DOI
- 10.1021/acsptsci.8b00036
- PMID
- 31559394
- PMCID
- PMC6761833
- NLM abbreviation
- ACS Pharmacol Transl Sci
- ISSN
- 2575-9108
- eISSN
- 2575-9108
- Publisher
- American Chemical Society
- Grant note
- DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: NS075599; DOI: 10.13039/100000005, name: U.S. Department of Defense, award: W81XWH-16-1-0071, W81XWH-16-1-0211; name: Veterans Affairs Medical Center, award: 1I01RX002101
- Language
- English
- Date published
- 02/08/2019
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070957402771
Metrics
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