AAN 2026 | Reflecting on the success of CGRP-blocking drugs for migraine treatment

Yeah, so this has been a bench-to-bedside success story that began way back decades ago, but because of all the work done by many labs, not just mine, but many other labs, particularly Lars Edvinsson in Sweden, Peter Goadsby in England and at UCSF, now back in England again. Messoud Ashina, Jes Olesen, I want to give credit. There’s a lot of labs who’ve worked on CGRP. And it’s their work that have really pushed this concept that this little neuropeptide, just 37 amino acids, could be so important in migraine pathology. And the genesis of that thought really was remarkably naive, but spot on, because it’s a vascular acting agent. And migraine historically is viewed as a vascular headache. It’s still controversial how much of the headache contribution comes from the vasculature or from the neuro part of it. So I think it’s going to be both. That’s my simple answer right there, both neuro and vascular. But because of CGRP’s action on the vasculature is why a lot of attention was focused on it. I think CGRP’s action, as I just mentioned, in the glymphatic system and the lymphatic systems, as well as on nerves directly, all are part of migraine. But anyway, that’s the history. A lot of great labs working on CGRP’s vascular actions and started looking, could this be involved in migraine? Pioneering work by Edvinsson and Goadsby’s labs showed that CGRP is elevated during a migraine attack. Jes Olesen did the key experiment back in 2002, injecting CGRP into brave volunteers in Denmark. These people, they are brave people. They have something injected that may give you a migraine, and they got migraines. And Messoud Ashina has carried the ball on that. So really then that led to the obvious question, well, let’s block CGRP. And I started first studies back in 2004, and finally in 2018, the first drug. So it takes a while, but four companies pushed it through, and we now have eight drugs that block CGRP action. I remember being asked, would this be safe to do? And I really don’t know, is what my answer was. I said, I think it’ll be safe because of compensation by other peptides. CGRP is a member of a family of peptides that have overlapping activity. If you’re only blocking CGRP and its receptor, then these other peptides should be able to compensate. But you don’t know. And we got really fortunate. I feel very, very lucky that the drugs have been as safe as they have been so far. So they are very effective, not for everybody, but there’s nothing better than when I get somebody telling me that their life was changed. So I’m not a clinician. My patients are all mice, but people talk to me about their migraines. And here work on migraine. And they say, once I started taking the CGRP drug, my whole life changed. I got my life back. So it’s been very rewarding for me personally and for my lab that these drugs have been so successful.

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