Could Antibodies Treat Migraines?

This article was originally posted on RealClearScience.

Migraines are just awful. It is very difficult to express in words to non-sufferers what a migraine is like. However, if you could imagine a vice rhythmically squeezing your brain every second for several hours (or days), that is roughly what a migraine feels like. For some migraine sufferers, such as your humble correspondent, it is even possible to feel your heartbeat in your brain, with each pulse bringing a throbbing pain.

Migraines appear to result from activation of the trigeminal nerve, located in the brain and face, which results in the release of small proteins (neuropeptides) that trigger inflammation and swelling in nearby blood vessels. The end result is pain. (See this excellent graphic summarizing the molecular mechanism of migraine.)

People who suffer from migraines usually have a war chest full of medications to help prevent or treat them. My personal toolbox, which I carry around in a little bag like a sickly octogenarian, contains Excedrin Migraine (which contains aspirin and acetaminophen), sumatriptan, and eletriptan. Though these drugs have different mechanisms of action, they share two major things in common: (1) They reduce inflammation (except acetaminophen) and, in the case of the two triptans, reduce vascular swelling; and (2) They are small molecule drugs.

Recently, some migraine research has shifted away from small molecule drugs to focus instead on antibodies, the immune system proteins typically thought of as microbe fighters. In fact, according to a recent article in Nature Biotechnology by Gunjan Sinha, four different monoclonal antibodies — all of which block the same neuropeptide (CGRP) — are in various phases of clinical trials. Because CGRP causes blood vessels to swell and is involved in pain transmission, blocking the protein (or its receptor) with an antibody should help stop migraines.

Results have been modest but encouraging. Unfortunately, small molecule drugs (which can be put into pill form) that target CGRP don’t work. Thus, research into CGRP blockers will likely continue to focus on antibodies, which must be injected and will cost patients upwards of $5,000 annually. Consequently, only the most serious migraine sufferers will benefit from this line of investigation. “Amateur” migraine sufferers, such as me, will have to be satisfied with the tools we already have.

Source: Gunjan Sinha. “Migraine mAbs crowd into late-stage trials.” Nature Biotechnology 33, 676–677 (2015). doi:10.1038/nbt0715-676c  Published online: 08-July-2015.