How to get rid of migraines: The most promising new treatments
Migraines affect 6 million people in the UK and can have devastating consequences on sufferers' lives.
For centuries, scientists have debated whether migraines are caused by blood vessels in the head expanding or by some malfunctioning of our nerves. Over the last few decades, however, a more nuanced picture has emerged. A migraine attack starts when the trigeminal nerve, a big pain-sensing nerve in our heads, is stimulated.
The source of that stimulation is hard to pin down but some people who get migraines find they are triggered by caffeine, stress or lack of sleep. The trigeminal nerve sends chemical signals to the protective layers that wrap around the brain.
The signals are vasodilating, meaning they cause blood vessels in some of these layers to expand. Together, the expanding blood vessels and the pathways of nerve fibres connected to the trigeminal nerve, which also reach deeper into the brain, are thought to cause the pain.
Thanks to King’s College London neurologist Prof Peter Goadsby and colleagues, we now know more about the chemical messengers responsible: neuropeptide molecules called calcitonin gene-related peptides (CGRPs), which are now the focus for new treatments.
But Goadsby says that we do currently have enough of an understanding for a coherent explanation of what’s happening and, crucially, to improve treatments.
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One aspect that we’re just getting to grips with is the genetics - some people are more susceptible to migraine than others but it’s not clear why. A 2022 study in over 100,000 patients pinpointed 123 different genes associated with migraine, 86 of which were previously unknown.
“Not every migraine patient has every gene, so it’s complex,” explains Mikko Kallela from the University of Helsinki, who worked on the study. “And that also fits very much to the way migraine patients respond to treatment.”
Since the 1990s, we’ve relied on drugs called triptans to treat migraines. These target serotonin receptors in the brain and are thought to work by constricting blood flow and preventing the release of neuropeptides involved in migraine. We are now, though, starting to capitalise on some of the research into the mechanisms that trigger and drive migraines, with the last five years seeing new drugs reaching the market.
Some of them, like erenumab, are human antibodies that bind the receptors for CGRPs, blocking them from triggering the migraine. These are given as monthly injections. Other drugs called gepants bind the same targets but consist of smaller molecules. These are pills that can be taken daily.
The gepants are the first drugs that seem to be beneficial both for an ongoing migraine attack and for preventing future attacks from happening – previously, drugs have only been prescribed for one or the other. Because there are no side effects from overuse, patients can take more or less depending on their needs.
“So the idea that you could tailor the therapy on a day-day-day, week-to-week basis with these new therapies is quite revolutionary,” Goadsby says, suggesting a patient could decide to take a tablet in the evening if they knew they needed to do something important the next day.
The difference that CGRP inhibitors have made is “very, very significant”, according to Kallela, who sees about half of his patients lose half of their migraine days. For the 1 to 2 in 100 people in the general population who experience at least 15 migraine days a month – chronic migraine sufferers – the benefits can be life-changing.
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But as it currently stands there is no known cure for migraine. Even if we are seeing a lot of progress in treatments, 'curing' migraines is a very big ask, especially when we don’t have all the answers as to what causes them in the first place. However, according to Goadbsy, we could see more progress in prevention by focusing our efforts to understand migraines on the 'premonitory phase' – the prelude to the headache, which for many people brings mood changes, yawning, tiredness and other symptoms.
This phase can last a couple of days. “If we could develop treatments in that phase, then it's perfectly plausible to think that we could start to eliminate the actual pain phase,” Goadsby explains, adding that it could be a way to “head off attacks before they become troublesome.”
Another approach that may start to make more of an impact in the near future is one of personalised medicine. We’ve known for ages that what works for one person doesn’t necessarily work for the next person, but as our understanding of the genetic components and molecular mechanisms that contribute to migraine expands along with the suite of different drugs targeting them, we may be better able to use this to the patient’s advantage, tailoring treatment regimens to the individual.
Intriguingly, some of the known genes pulled out in Kallela’s 2022 study were targets for existing treatments – the CGRPs, for example. This suggests we might be able to mine for new migraine targets among the 86 genes whose functions are unknown.
However, because of the way that people who get migraine are genetically predisposed to them, it’s hard to imagine “curing” them completely. People who get migraines may always go back to having them if they stop taking their medication, according to Kallela, but he remains “very optimistic” about the prospects for treatment. “You cannot cure migraine,” he says. “But in a way, you can take away the attacks.”