Treating Migraine Early: A Conversation with Jessica Ailani

“With migraine, not only can you take care of someone early in their disease, but you can also help protect the brain from other brain disease processes; migraine comes along with other neurological conditions like epilepsy, Parkinson’s, and stroke. But if you put patients on a good path of taking care of the brain and having healthy life habits, that could potentially prevent some of these problems. I think that is super exciting as a neurologist.” – Jessica Ailani

Jessica Ailani, MD, is a professor of clinical neurology at MedStar Georgetown University Hospital in Washington, D.C. She’s also the director of the Georgetown Headache Center, where she works as a clinician and studies migraine treatments.

Among other research projects, Ailani works on understanding situational prevention – a treatment approach aiming to stop migraine in the earliest stages of an attack. Ailani and her colleagues recently published a study of over 55,000 patients showing that people who used remote electrical neuromodulation at the start of a migraine attack had fewer migraine symptoms than people who treated their attacks at later stages.

Ailani is now testing whether situational prevention works with other preventives, including the CGRP inhibitor rimegepant. She recently sat down with freelance science journalist Freda Kreier to talk about situational prevention, and her role in shaping the American Headache Society’s research priorities. What follows is an edited transcript of their conversation.

How did you become interested in migraine?

As a young child, I found the brain very fascinating. Going into residency, I was focused on maybe going into the epilepsy field. But as I started residency, most of what we saw in the neurology clinic was headache and back pain.

Headache patients tended to be young women who were really struggling with day-to-day activities. Back when I was a resident, we only had two or three options to offer people, but it was pretty powerful how those options could completely change a person’s life. So I pursued a headache fellowship, and within weeks I was like, ‘Oh my gosh, this is a perfect fit for me.’

With migraine, not only can you take care of someone early in their disease, but you can also help protect the brain from other brain disease processes; migraine comes along with other neurological conditions like epilepsy, Parkinson’s, and stroke. But if you put patients on a good path of taking care of the brain and having healthy life habits, that could potentially prevent some of these problems. I think that is super exciting as a neurologist.

You have an interest in situational prevention, where the aim is to treat migraine early. How well do we understand this treatment approach?

The anti-CGRP drugs, particularly rimegepant, really lent themselves to the idea of early treatment. With rimegepant, if you treat at the onset of migraine, when you’re having non-pain symptoms like nausea, light sensitivity, sound sensitivity, and irritability, it can stop or reduce headaches. It can improve the prodromal symptoms as well, which are very disabling to patients.

So, what if we move the time window a little earlier? If a person has a very reliable, reproducible situation or trigger that happens, such as religious holidays where you must fast the whole day, could a treatment be given in advance to stop that migraine from happening?

At MedStar right now, we’re doing a study looking at preemptive triggers, or situations that can occur and trigger a migraine attack. But first the patient must prove that these are reliable situations that occur before they have a migraine attack.

Jessica Ailani

Tell me more about the study you’re currently running.

We’re looking at people who have two to 10 migraine attacks per month. These patients have reliable triggers like alcohol, long flights, or high-intensity workouts. We have them decide on a single trigger and give them two months to experience the trigger as is. Then, once they’ve experienced the trigger three times, we take a look and make sure that it’s been a reliable cause of migraine.

Then they can enter the part of the study where they’re given rimegepant. When they’re exposed to the same trigger, they take the rimegepant an hour or two hours before the situation occurs – for instance, if they know they’re going to have alcohol tonight, they take the drug two hours before – and then we see what happens. In clinical practice, we have seen that treating with rimegepant during situations such as these can prevent migraine from happening. We wanted to show our clinical findings in a more controlled setting.

What would you like people to know about situational prevention?

It would be great for them to know that there is research on the horizon. And I think it’s important to talk to patients more about the idea of situations they know are going to cause an attack.

Also, science is extremely important in the headache field; it’s what keeps the clinical side going. And I hope that people understand that even in a difficult scientific climate, the research still has to move forward.

Switching gears, you recently were involved with the American Headache Society’s Headache Research Priorities initiative [see MSC related news]. How did you become a part of this effort?

I’ve been a member of the American Headache Society [AHS] for almost two decades now; I’m currently the treasurer, so I’m pretty involved. AHS created a research committee to ensure that some of the research work of the society was being highlighted. One of the things that the research committee was tasked with was creating an article that describes where we think research should be going over the next decade [these research priorities were published in the fall of 2024; see here].

This is probably one of the hardest things I’ve worked on in a long time. It’s pretty easy to say where we are right now, and where we think treatments might go in five years, but it’s a lot harder to sit down and ask where we want things to go if we had unlimited funding – absolutely anything we could have in the world – because I don’t usually think that way.

Then there was an open comment period for AHS members, and then at NIH for anyone to submit comments and questions. We got lots of feedback from patients, organizations, the public, and from our members.

How did the public comments change the research priorities?

What we were missing was thinking beyond migraine. Many comments we received asked why the focus is always on migraine – what about other headache disorders? This is an issue generally; we don’t get a lot of funding for headache disorders, and when we do get funding, it’s focused on migraine.

We naturally start thinking about research in migraine, but the truth is, we need a lot more work across the board in the over 200 headache disorders affecting patients. There are headache disorders that nobody’s ever even looked at. As clinicians, we just try to reapply the research we have in migraine to other headache disorders and hope for the best. This is really sad and difficult; for patients, it’s annoying and frustrating. But if there’s no funding, how do you study this stuff? It’s really tough.

If we’re wrong about the mechanisms of migraine, then we’re going down the wrong path for treatment. So part of these discussions was focused on how we need to think about other non-migraine headache processes.

What are some things that stand out to you about the research priorities effort?

We must think about what’s actually happening in a person’s nervous system that’s causing the headache and focus treatments on these processes.

We also don’t have a lot of data on layering treatments – does that work better? And how does this all relate to adding something like neuromodulation to a medication? We don’t really have studies here, but we need that information.

And then, how can AI help us generate information? Can it go through databases and look at information, see what’s missing, and maybe bring us to new information faster? It’s been nice to see some of those studies being done now and in the last several years. When you talk to people doing the work, they say it takes the machine seconds to generate some of the data, and it takes people a year of going through the data by hand. So how do we make AI methods more available? How do we make it easier to use those tools to study some of the things that we’re trying to study?

How will the research priorities be used?

The hope is that they will guide where the research should go. So when the NIH is looking at giving grants, they’ll look at the list of priorities and award grants that focus on this research.

It’s hard to say if that’s happening, because so much federal funding has been put on hold. I don’t think any of us had any idea where things were going. I really hope this was not work that we did in vain, and that it won’t be ignored now.

Do you think we’ll be able to meet these goals with current funding challenges?

Many of my colleagues lost their grants, but there are new grants becoming available that are not NIH funded. The hope is that these research ideas will become part of these other grants. The AHS now has many more research scholarships available than they’ve had in the past; they’re seed dollars to get things started. The American Academy of Neurology has similar types of grants, and so does the International Headache Society. We’re hoping that, over time, smaller organizations can start to pick this up and give small seed dollars so that people can keep research going through this period. We’re trying our best for our patients to keep the hope going.

The other hope is that, because headache is a chronic condition, if the government is really looking at resolving chronic medical conditions, then migraine and other headache disorders should be number one on their list, because these conditions affect working adults who must take time off from work and then become unproductive. If your goal in government is to take working adults and keep them working, then there is no better disease to focus your energy on than this.

Freda Kreier is a science journalist based in Corvallis, Oregon.

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