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Reader response: Potential for treatment benefit of small molecule CGRP receptor antagonist plus monoclonal antibody in migraine therapy

  • Vinod K. Gupta, Physician-Director, Migraine-Headache Institute, Gupta Medical Centre (New Delhi, India)
Submitted January 14, 2020

I read the article by Mullin et al.1 The premise that CGRP plays a crucial role in migraine pathophysiology1 will take meaning only when CGRP-release robustly explains: (1) the genesis of the scintillating scotoma and the lateralizing headache of migraine; and (2) spontaneous release of CGRP with cut-off at onset and offset of migraine headache, respectively. Programmed release of CGRP at puberty/adolescence and menarche/menstrual cycles as well as programmed cut off in the second and third trimesters of pregnancy, menopause, and advancing age (with exceptions) must be knit into the scientific fabric of migraine.2 Since alcohol and sleep are closely linked to triggering of migraine, their link to CGRP would be equally essential. As sleep also relieves most migraine attacks, does sleep cut off CGRP release? Since psychosocial nonoxidative post-stress phase is the commonest precipitant of migraine attacks, is there a link of the post-stress phase with CGRP release? Such considerations are not mere technicalities but lie at the heart of the migraine conundrum.3

Therapies involving CGRP highlight the typical cart-before-the-horse pattern not uncommonly seen in the science of migraine. Closure of patent foramen ovale4 and botulinum toxin administration5 are two other high-profile therapeutic strategies that were predicted to fail.4,5

Disclosure

The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.

References

  1. Mullin K, Kudrow D, Croop R, et al. Potential for treatment benefit of small molecule CGRP receptor antagonist plus monoclonal antibody in migraine therapy. Neurology 2020 Epub Jan 13.
  2. Gupta VK. Reader response: Calcitonin-gene related peptide antagonism to prevent migraine: Hope, hype, and hokum. Neurology. Published September 07, 2017. Available at: https://n.neurology.org/content/calcitonin-gene-related-peptide-antagonism-prevent-migraine-hope-hype-and-hokum.
  3. Gupta VK. Reader response: Vascular safety of erenumab for migraine prevention. Neurology. Published 24 December 2019. Available at: https://n.neurology.org/content/reader-response-vascular-safety-erenumab-migraine-prevention.
  4. Gupta VK. Patent foramen ovale closure and migraine: science and sensibility. Exp Rev Neurother 2010;10:1409–1422.
  5. Gupta VK. Botulinum toxin—A treatment for migraine? A systematic review. Pain Medicine 2006;7:386–394.

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