New Preventative Treatment for Migraine Sufferers

Review of the recent trial of Fremanezumab in the prophylactic treatment of migraines.

A recent trial of a humanised monoclonal antibody has shown potential in the preventative treatment of migraines in chronic migraine sufferers. It is hoped that the drug can be used to treat the notoriously debilitating Cluster headaches. Fremanezumab is in the class of drugs that block the CGRP pathway. Other drugs with this mechanism of action already on the market include Eptinezumab, Erenumab and Galcanezumab.

The new treatment centres around the use of a humanised monoclonal antibody known as Frumenezumab to target both alpha and beta calcitonin gene-related peptides (CGRP) which are implicated as a catalyst for migraines. as already mentioned, other drugs are available that perform this action, however, this recent phase III trial has demonstrated a significant improvement in resolving migraines with a single dose given by monthly injection saw a reduction of migraines by 50%. Another group was given a quarterly dose and also reported a 50% reduction of migraines, indicating that increased dosage may not be necessary, or otherwise may not elicit a significant increase in therapeutic effect.

Calcitonin Gene-Related Peptide

Calcitonin gene-related peptide (CGRP) is a peptide in the calcitonin family which exists in two forms, ɑ-CGRP and β-CGRP. ɑ-CGRP is a 37-amino acid peptide synthesised by the by the alternative splicing of the calcitonin.CGRP gene in chromosome 11. Less is known about β-CGRP except that it differs by 3 amino acids in the peptide and is encoded by another gene in the vicinity of ɑ-CGRP1.

CGRP is produced by both peripheral and central neurons and is a potent vasodilator, but also functions in the transmission of pain. The cell bodies on the trigeminal ganglion are thought to be the main source of CGRP. Its primary function is believed to be in regulating cardiovascular homeostasis as well as playing a role in nociception.

CGRP has been found in increased levels in patients with chronic migraines and has been implicated in the condition as the causative factor, however, this remains to be conclusively determined2. CGRP’s role in both nociception and cardiovascular regulation is believed to be the catalyst for migraines by binding with receptors in the meningeal vessels, leading to vasodilation and increased pain signalling in the trigeminal ganglion324.

Fremanezumab 

The new drug known as Fremanzumab binds with free-floating CGRP and prevents it from binding to receptors, stopping the migraine chain before it can start. As the drug is still experimental, not much is known about its specifics.

Conclusions

The results of the study make a promising step forward in the treatment of migraines, and cluster headaches by extension. Further research into the role of CGRP in the genesis of migraines may yield improved treatments in the future. The use of a maintenance dose of the drug could bring the treatment of migraines into an accessible realm for many sufferers. Similar to contraception, a simple maintenance dose administered quarterly (or monthly) by a GP may be enough to restore at least some level of quality of life to many sufferers.

Read the article on NEJM now

References

1.
Rezaeian A, Isokane T, Nishibori M, et al. alphaCGRP and betaCGRP transcript amount in mouse tissues of various developmental stages and their tissue expression sites. Brain Dev. 2009;31(9):682-693. [PubMed]
2.
Durham P. Calcitonin gene-related peptide (CGRP) and migraine. Headache. 2006;46 Suppl 1:S3-8. [PubMed]
3.
Arulmani U, Maassenvandenbrink A, Villalón C, Saxena P. Calcitonin gene-related peptide and its role in migraine pathophysiology. Eur J Pharmacol. 2004;500(1-3):315-330. [PubMed]
4.
Goadsby P, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990;28(2):183-187. [PubMed]

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