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While the exact reason is unknown, it is thought to be triggered by hormones, genetics, or a combination of factors. CGRP blockers act like a "dimmer," reducing CGRP activity. “One class of CGRP blockers binds to CGRP proteins, mopping them up like a sponge, meaning that that CGRP is not able to act on its receptor, reducing the number of signals that are sent,” Debbie says. Drugs that dampen CGRP activity have been life-changing for many, but unfortunately, they don’t work for everyone. “CGRP is one of the key players in driving migraine. However, migraine is a condition of many layers, with lots of different factors combining that under the right conditions can trigger an attack,” Debbie says. “We don’t have all the answers yet. Here in New Zealand, we are part of global research efforts to learn more about how CGRP pathways work at a molecular level, and if there are further opportunities to reduce pain signals in migraine using this approach.” The uptake of CGRP inhibitors has been slow, Debbie says, partly due to cost, and lack of patient-access and awareness. But there has been a flurry of international drug approvals targeting the CGRP pathway, so expect to see new iterations in the coming years. For those with migraine who find no relief from triptans or CGRP inhibitors, Peter highlights a new treatment currently in early clinical trials. “The next big thing is going to be something that targets PACAP (pituitary adenylate cyclase activating polypeptide).” Similar to CGRP, PACAP levels are elevated during migraine attacks. This is thought to contribute to the activation of the trigeminal nerve, which plays a central role in migraine pain. Peter emphasises that when migraine sufferers have an attack, they should never think that there is no way forward – because there is. “There are people beavering away in laboratories, perhaps not enough people, but you should never imagine there is no interest in migraine in the scientific community. “You should never have to think that no one believes you've got the condition, because we do, and the science is crystal clear. And if any of my colleagues in medicine have not treated you very well, I apologise. We should do better.” “...migraine is a condition of many layers, with lots of different factors combining that under the right conditions can trigger an attack...” P rofessor Debbie Hay Dr Fiona Imlach, Migraine Foundation co-founder. Headlines 7