Making Progress: The Australian Treasury’s Loss Becomes the Headache Field’s Gain – A Chat with Peter Goadsby

“The first thing is the growth in the field. It’s now respectable to do headache! Every time I go to a neurology meeting now, there is a talk about headache, and it’s treated like a normal part of neurology. We’ve finally realized that we need people to look after those with headache disorders. And seeing migraine come in from the cold, so to speak, is so important because it means patients get treated better.” – Peter Goadsby

Peter Goadsby is director of the National Institute for Health Research at King’s Clinical Research Facility and a professor of neurology at King’s College London. His research ranges from the basic mechanisms of primary headache disorders, including migraine and cluster headache, to translational work leading to better management of those conditions. His work elucidating the role of calcitonin gene-related peptide (CGRP) in migraine helped paved the way for a new and effective class of medications to prevent and treat this form of headache.

In this Migraine Science Collaborative interview, Goadsby speaks with freelance writer Kayt Sukel about the surprising way he got into medicine, how his work on CGRP started from a research conference conversation, and why physicians need to get their own house in order to reduce headache stigma. The interview has been edited for clarity and length.

What first inspired you to pursue research in the headache field?

I hadn’t intended to go to medical school – I wanted to be Treasurer of Australia. I didn’t even do biology at school; I did economics, mathematics, and chemistry. I planned to go into economics and law and subsequently applied to study that. But in Australia, you take a final exam in high school and, based on your score, you’d be matched with a particular field after ranking different things you wanted to do.

When the results came out, my mother thought I hadn’t done very well. I thought I scored well and told her I could do anything I wanted, even medicine if I wanted to. In a fit of pique, I changed my allocation to medicine for my first pick; number two was economics and law. I didn’t think much of it. Then, about a month later, I received word I’d gotten into medical school, which was a considerable surprise. I couldn’t change at that point, since in Australia, at university, you have to make a start if you want to make a change.

I didn’t like medicine for a while, I have to say. But when topics involving the brain came along, I got more interested. So I stayed with it and not long after, my mentor, Jim Lance, gave a talk about migraine. At the time, the vascular hypothesis was big in the field, but I thought the explanation of it was not logical. I went up to him after the talk and told him as much, and he rather politely told me my thoughts were interesting and perhaps I could come and help by doing some research.

I ended up taking time off from medical school to do a PhD, and that was it for me – I found something I was really interested in, and the research was very exciting because from time to time you would know something no one else knew, because you had just worked it out. I decided to be a neurologist with an interest in headache. I thought it was a place where I could make a difference, and if you want to make a difference you have to apply your attention with focus.

Peter Goadsby

What were some of the research questions you were trying to figure out at the beginning of your career?

As I said, at the time, the vascular hypothesis of migraine was very popular. It always struck me as a very strange idea. What we were trying to understand was if you could model nerve pathway activation or inhibition in animals to model parts of what was going on in humans. It was early work in what people now call the trigeminovascular system. Then, after meeting Lars Edvinsson in Sweden, I started thinking about how we could start doing this kind of research in humans. I’d been at the bench for four years at that time and while I was making some progress, the rubber doesn’t really hit the road until you’ve seen whether what you’re working on makes any sense in humans.

Edvinsson gave a talk about the way the trigeminal system protected cerebral circulation during hypertension; he talked about neuropeptides being protective. It occurred to me during the talk that maybe migraine, in some form, is protective or an exaggeration of normality, so to speak. We chatted after his talk, and I told him I had an idea about how we could take the things he was thinking about and the things I was thinking about and try to do a study to see if CGRP peptides had a role in humans. We started collaborating in 1985, and the rest is history.

How do you define your goal in the headache field?

The overarching goal has always been to make the world a better place for people with headache disorders. That’s the mission statement. That could be about understanding a disorder or finding ways to create new treatments. Take the work we’ve done over the past 15 years in premonitory symptoms. Twenty years ago, if you said you wanted to study premonitory symptoms, the grant reviewer would say it’s a complete waste of time. These days, I think people have started to realize that these symptoms are an important component of disability. They allow you to shed light on what’s happening early in an attack. And as we’ve seen from the PRODROME trial, we can actually treat during the prodrome.

It’s gone from, “That’s a really stupid idea; you are wasting your time,” to something that helps patients. And it’s also something that helps people to understand their disease better. A person who lives with migraine wants to know why they may be thirsty before an attack. There’s value in knowing more about the disease and that there’s good biology behind what they are experiencing. They value that. But of course patients value getting better the most.

You’ve made contributions to understanding both migraine pathophysiology and treatment. Science usually advances incrementally, but is there a particular study that you think really kicked the ball forward?

The Annals of Neurology paper that showed CGRP elevations, and not substance P or neuropeptide Y, were related to migraine was it. It really took the work that Edvinsson and I had been doing for about five years from an interesting laboratory phenomenon to something that we could show was happening in humans. From that point on, it was only a matter of time until some company picked it up, got off the triptan excitement bandwagon, and got the chemists involved so a treatment could be brought forward. That was quite exciting.

What is the state of the migraine field today? What are you most excited about?

The first thing is the growth in the field. It’s now respectable to do headache! Every time I go to a neurology meeting now, there is a talk about headache, and it’s treated like a normal part of neurology. We’ve finally realized that we need people to look after those with headache disorders. And seeing migraine come in from the cold, so to speak, is so important because it means patients get treated better.

In terms of what’s exciting me on the understanding side of things, the results from the pituitary adenylate cyclase-activating polypeptide [PACAP] study in the New England Journal of Medicine show it’s an interesting prospect for another treatment [see MSC related news]. It’s in the pipeline of possibilities waiting for chemists to sort out the details. We’ve got some new targets. And the current work in the field shows that if you understand the biology well enough, and you can get some idea of the targets, you can eventually wear down the problem to have new treatment options. Because, as exciting as it is to see people who are doing well on gepants, there are plenty of people who do not respond to current treatments. We’ve got a lot of room to move and I see a lot of potential for that.

Are there any particular gaps you see in the field right now?

Money. When you look at what NINDS [National Institute of Neurological Disorders and Stroke] is doing, it’s wholly inadequate. It’s just not right that the research spend on a disorder that affects so many taxpayers – because migraine is a disorder in 18- to 65-year-olds – is only about a $1, $1.50 per taxpayer. On what planet is that reasonable? All they have to do is say, we’ll give $5 for each taxpayer. It wouldn’t be charity; it would be an investment. Because you could help more people, they would end up economically more active, and they’d pay more tax. Practically speaking, the more people with migraine who are engaged, and living well, and creating economic activity, the more it would help us all. As you can see, I never lost my interest in economics. The vast under-resourcing of research compared to the size of the problem and the potential for return to the greater community is just silliness to me.

You’ve worked on understanding different types of headache. Is there a condition that you find of particular interest?

Hemicrania continua and paroxysmal hemicrania are exquisitely responsive to indomethacin, but not other non-steroidal medications, and we don’t know why. Just last week, I was talking to a physician looking after a patient who was on indomethacin and had a gastric bleed that put him in the hospital. What do you do next? You’ve got a condition that is exquisitely responsive to something that could kill a proportion of the people who take it. So I’ve got some projects in trying to understand where we should go with indomethacin-sensitive headaches.

The other condition I think a lot about is cluster headache. I remember the first person I saw with cluster headache having an actual attack. I remember thinking, “This is very bad; I should do something about this.” It’s such a horrible condition, and we have very little in the way of treatment, particularly for prevention. It gives us a wonderful biological challenge. This is a condition that occurs at the same time every year, at the same time every day, then stops and comes back. It has to have some wonderful fundamental bits of biology that we can figure out, and getting that understanding might be able to help a lot of people.

What changes have you observed, if any, in migraine stigma?

My overarching prejudice is that biology ultimately fixes stigma. The more concrete of an understanding we have of a problem, the less people can stigmatize it. And, frankly, the biggest stigma is ignorance. Unfortunately, humans have always been like this. What we didn’t understand, we used to burn. Historically, communities used to burn epileptics because they didn’t understand epilepsy. Now we’ve stopped burning people, which is progress, but we still criticize.

Knowledge helps stigma. And, over time, three things have helped mitigate stigma in migraine. First is the work that the Dutch researchers did showing the familial hemiplegic migraine gene. It’s hard to argue with genetic differences. Functional imaging has done a lot, too. I can take 20 people, trigger their migraine, and show a constellation of changes in their brain. They didn’t make it up; you can see it happening. And the third thing that has helped to combat stigma is the treatments we develop. Migraine treatments are useless for broad pain problems. They are mostly useless for anything but migraine. Randomized, placebo-controlled trials are some of the strongest de-stigmatizing things because they have provided new facts that people can’t argue with. Take the CGRP trials. The trial results are consistent, and there have been more than 20 of them now. They all show the same thing. How is that not biological?

But, all that said, we haven’t really kicked the stigma problem far enough out of the park. One of the most disturbing pieces of data I’ve seen was from a survey done by the European Migraine and Headache Alliance [see MSC related interview]. Something like 20% to 25% of the patients they surveyed said they experience the most stigma from physicians. That’s not good because physicians ought to know better.

As physicians, we need to put our own house in order. We cannot expect everyone else to help us with a condition if physicians are stigmatizing patients. And worse, as physicians, we take an oath to do no harm. That’s our job. That’s what we swear. So even if a doctor can’t do much about a condition, the least he or she can do is not make it worse. Being a physician is firstly about being kind. Even if you don’t understand the condition, just be kind.

You’ve had a long and storied career. What do you hope your legacy will be?

A lot of well-trained people who are interested in migraine. I’ve trained quite a few, and I like to think that my legacy will be the next generation who will do more than I ever got done and make the world even better for people with headache disorders.

Kayt Sukel is a freelance writer based outside of Houston, Texas.

Image credit: peshkov/123RF Stock Photo.