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  • Year in Review
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HEADACHE IN 2018

Getting closer to a cure for migraine

In the past few years the scientific community has witnessed a prodigious surge in research activity, publication of data and progress in understanding the mechanistic components of migraine. This renaissance is the result of efforts initiated decades ago that are finally being translated into benefits for individuals affected by this disease.

Key advances

  • Trials have demonstrated that monoclonal antibodies that target calcitonin gene-related peptide 1 induce marked improvements (>75%) among a small but meaningful proportion of patients with chronic migraine1 or episodic migraine2.

  • Noninvasive vagal nerve stimulation delivered with two short-duration stimulations at the neck level has proved effective in the treatment of migraine attacks: one-third of patients achieved pain-free status at 2 h (ref.4).

  • Preclinical data support the idea that pituitary adenylate cyclase-activating polypeptide and its G-protein-coupled receptors are viable targets for new migraine treatments8.

  • Intriguing findings obtained in a migraine-specific animal model point to another potential pathway implicated in migraine pain: inhibition of acid-sensing ion channels prevents cephalic allodynia10.

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Fig. 1: Mechanism of action of monoclonal antibodies that target calcitonin gene-related peptide 1.

References

  1. Ashina, M. et al. Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: a subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia 38, 1611–1621 (2018).

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  2. Stauffer, V. L. et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 75, 1080–1088 (2018).

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  3. Halker Singh, R. B. et al. Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab: post-hoc analyses from phase 2 trials. Cephalalgia https://doi.org/10.1177/0333102418772585 (2018).

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  4. Tassorelli, C. et al. Noninvasive vagus nerve stimulation as acute therapy for migraine: the randomized PRESTO study. Neurology 91, e364–e373 (2018).

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  5. Moeller, M., Schroeder, C. F. & May, A. Vagus nerve stimulation modulates the cranial trigeminal autonomic reflex. Ann. Neurol. 84, 886–892 (2018).

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  6. De Icco, R. et al. Peripheral vagal nerve stimulation modulates the nociceptive withdrawal reflex in healthy subjects: a randomized, cross-over, sham-controlled study. Cephalalgia 38, 1658–1664 (2018).

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  7. Vollesen, A. L., Guo, S. & Ashina, M. PACAP38 dose–response pilot study in migraine patients. Cephalalgia 37, 391–395 (2017).

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  8. Frederiksen, S. D., Warfvinge, K., Ohlsson, L. & Edvinsson, L. Expression of pituitary adenylate cyclase-activating peptide, calcitonin gene-related peptide and headache targets in the trigeminal ganglia of rats and humans. Neuroscience 393, 319–332 (2018).

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  9. Waschek, J. A., Baca, S. M. & Akerman, S. PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma. J. Headache Pain 19, 23 (2018).

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  10. Verkest, C. et al. Effects of systemic inhibitors of acid-sensing ion channels 1 (ASIC1) against acute and chronic mechanical allodynia in a rodent model of migraine. Br. J. Pharmacol. 175, 4154–4166 (2018).

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Correspondence to Cristina Tassorelli.

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Competing interests

C.T. declares that she has received fees for serving on scientific advisory boards for Allergan, ElectroCore, Eli Lilly, Novartis and Teva. R.D.I. declares no competing interests.

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Tassorelli, C., De Icco, R. Getting closer to a cure for migraine. Nat Rev Neurol 15, 64–65 (2019). https://doi.org/10.1038/s41582-019-0134-z

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