CGRP Antagonist based Migraine Treatment making noise at AHS 2014

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The CGRP or Calcitonin gene-related Peptide exists in two forms α-CGRP and β-CGRP both function similarly, but the difference is thus far indistinguishable besides the fact that the β peptide differs by a mere three aminos acids from it’s 37 amino acid brother peptide α. CGRP receptors are found throughout the body, suggesting that the protein may modulate almost all of the physiological functions in most likely all major systems (e.g., respiratory, endocrine, gastrointestinal, immune, and cardiovascular). Receptor antagonists may also have the potential of limiting the effects of CGRP, though one promising drug candidate in this class (telcagepant) was withdrawn by Merck Pharmaceuticals after phase III trials. I wrote about this earlier in the year but wanted to write more of an overview article about the topic as it was one of the major topics of discussion at the American Headache Society’s annual meeting in Los Angeles this year. It is attended by medical professionals only so I only have what information I saw through twitter but I assure you the live tweet coverage by Doctors Dawn Buse, Amaal Starling, Nate Bennett, and L. Charleston IV, MD. Here are some of the tweets about CGRP antagonists from the meeting:

CGRP antagonists are good to migraine treatment because they shut down the CGRP receptors which take in light and influence on how things are seen. However without it, people do see just as well as if it but are actually far less sensitive to light. Many migraineurs experience light sensitivity as a trigger, which is a reason why it’s good to shut down such a receptor. At least this is my novice level understanding of the matter.

A lot of questions still remain about CGRP antagonists and their use in migraine treatment. Headache specialists at the American Headache Society’s annual meeting are quite excited to be using a drug that’s actually been made to treat migraine for that purpose. Often doctors find themselves prescribing anti-seizure and anti-depressants to migraineurs but this drug could change all of that. In a recent 2014 study, released in The Journal of Headache and Pain, many CGRP antagonists were utilized on fresh brain slices prepared from a mouse to stimulate a CGRP release from the trigeminal terminals of the brain. Not only did they detect the release of the antagonist, the amounts detected were well over the necessary amounts. This is good news for those of us with migraines and cluster headache, Potassium induced calcium-dependent and reversible CGRP release seems like the best option thus far to a novice investigator like myself. Almost all of the other ways to release CGRP seem non-reversible and carry the risk of being inhibited in some areas of release by triptans.

For those who don’t quite know what triptans are let me explain the feeling of taking sumatriptan for example. You experience the quick shot then severe pain throughout your head and it feels like somebody is sitting on your chest, then suddenly you feel some relief. For me I’d go down only 1-2 pain level from an 8-10 in pain that I typically live with being a daily chronic migraineur. Let me explain triptans now in a more clinical way triptans are serotonin receptor antagonists. The brand names for them are Axert, Frova, Maxalt, Imitrex, and Zomig whilst the clinical names are in the same order almotriptan, frovatriptan, rizatriptan, sumatriptan, and zolmitriptan. These medications narrow or constrict blood vessels in the brain which relieves swelling. Unfortunately it isn’t completely clear how exactly they stop a migraine though none of them ever “stopped” any of my own attacks.

What do migraineurs think about the situation now that CGRP antagonists are being used on humans with excellent preliminary results? Especially since it seems the cardiovascular side effects are minimal or non-existent unlike with triptans?

I’d like to thank the American Headache Society for inspiring  me to write this article about CGRP antagonists and the hope for a new migraine based medication. I am happy to hopefully bring this to patients in simpler language they can clearly understand and have hope for in the future. Like me many have run the gamut on migraine procedures and medications coming up short and far from relief. I hope that this article will give that group back a glimmer of hope. Thanks for reading and I hope this article taught you a little bit about CGRP antagonists!

6 thoughts on “CGRP Antagonist based Migraine Treatment making noise at AHS 2014

  1. This is helpful. You are doing a great service to rewrite these articles in language we can all understand. Just trying to comprehend some of those medical journal articles is enough to give anyone a headache. I used to read a lot of medical journals. I am unable to take certain medications and classes of medications such as Triptans because of the medicines I need to be on for my kidney transplant. I have tried my share of anti-seizure and anti-depressant medications over the years. Looking forward to your version of such articles in the future.

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