New drugs, decades in the making, are providing relief for migraines.

Nancy Baum Lipsitz remembers the night the pain began. She’d had a glass of white wine with a friend and went to bed with a terrible headache. The next day, she still felt horrible, the beginning of what she called a “rolling tide” of near constant migraines and lower level headaches.

For three years she dealt with the symptoms. Sometimes she got tunnel vision, or a visual aura, a warning that a big headache was on the way. Those felt like “someone taking a pick and jabbing it through my nose and eye,” she said.

Then there was the vomiting, numbness and sensitivity to light and noise. Her speech slurred. Less severe headaches felt like a “hangover.” She stopped exercising, socializing and overseeing her 15-year-old daughter’s homework, relying instead on her daughter to take care of her, bringing an ice pack, medication or whatever else she needed when a migraine attacked.

“Everything you are as a human being gets stripped away,” Lipsitz said of what was ultimately diagnosed as refractory migraine. The one thing she did not give up was her work. As director of anesthesiology at Carnegie Hill Endoscopy in New York, she knew patients and staff depended on her.

“I am not going to let a migraine shut me in the bedroom,” she said. She showed up at 6 a.m., no matter the pain.

Migraine, a type of headache disorder that is distinguished from tension headaches by its pain, frequency, and the nausea and sensitivities Lipsitz endured, affects 10 percent of the world population and 29.5 million Americans, the majority of them women, often during the prime years of career and parenthood.

The cost, measured by direct health-care expenses, lost or poor productivity, and missed family involvements, affects children, too. A recent study showed increased anxiety and depression in adolescent children of parents with chronic migraine.

Swedish researcher Lars Edvinsson is credited with clarifying the role CGRP plays in the brain. On the wall behind him is an image of a vessel with CGRP positivity. (Jeppe Carlsen)

For years, treatment has been limited and primarily addressed symptoms rather than prevention. Migraine was thought to be “more of a hysterical woman’s disease and not given the respect it really deserves,” said Susan Broner, Lipsitz’s neurologist and medical director of the Headaches Program at Weill Cornell Medicine/New York-Presbyterian. Funding for research has typically been disproportionately low compared with the disease’s effect.

But new treatments, decades in the making, are giving patients more options to manage what is now understood to be a complex neurological disease. This year, the Food and Drug Administration approved three drugs meant to prevent migraines and those, along with less expensive and less invasive techniques to stimulate the body’s response to pain through neurostimulation, are giving headache specialists and the patients they treat optimism.

“The entire field is changing,” said Stephen Silberstein, director of the Headache Center at Jefferson Health in Philadelphia. “There is a revolution in migraine.”

In July, Lipsitz started monthly injections of erenumab-aooe (Aimovig), one of the three new drugs targeting the pain transmitting signal, calcitonin gene-related peptide (CGRP) or its receptor. Monoclonal antibodies, such as the one in her medication, work by blocking CGRP, the chemical involved in migraine.

“I see it as being my savior, my hope,” she said. She has had more days of feeling good in three recent weeks than she had in the previous three years.

The treatment has not eliminated all pain. Lipsitz has not been able to wean off other medications. But the new therapy has given back much of what migraines had taken away, especially time with her husband.

Preventing migraines with CGRP antibodies opens up a new world, Broner said. “It is the first time we have a medication developed specifically for the mechanism of migraine, which means we are really targeting the disease state itself.”

For decades, doctors treated migraines with therapies developed for other diseases, using blood pressure medication, anti-seizure drugs, anti-depressants and even OnabotulinumtoxinA (Botox). Lipsitz has been on all of these, finding some relief but also reduced effectiveness over time, or side effects and fatigue. The nonsteroidal anti-inflammatory drugs she took for breakthrough pain gave her a bleeding ulcer and kidney damage.

The new drugs are unique because they not only prevent (as opposed to abort) migraine attacks but also are well tolerated.

“That’s the key,” said David Dodick, a neurologist and headache specialist at the Mayo Clinic in Arizona. “If I give you something to take and it’s effective but you can’t tolerate the side effects, you’ll stop it.”

The recent shift in migraine treatment comes from a change in understanding what causes them, he said. Migraine had previously been considered a blood vessel problem. It was “really a nerve problem,” he said.

Credit for understanding the role CGRP plays in the brain goes in large part to the Swedish researcher, Lars Edvinsson, who began his work 30 years ago. Back then, he could not buy the peptide, so he built it, connecting 37 amino-acids-like pieces of “a Lego” construction, he said.

In 1990, Edvinsson and a colleague, Peter Goadsby, looked for CGRP in patients during a migraine attack, taking blood samples from the jugular vein, near the point of release in the brain, instead of the arm, where levels are diluted. They showed CGRP was the only neuropeptide released during the headache phase.

Some of the new antibody drugs — galcanezumab, (Emgality), fremanezumab (Ajovy) and eptinezumab, now in phase 3 clinical trials and administered as a quarterly infusion — target CGRP directly, while erenumab (Aimovig), targets the CGRP receptor, the means by which the protein transmits pain. Blocking the receptor is like putting gum in a lock, Dodick said.

“You can’t get the key in anymore. You can’t open the door,” he said.

Because these antibody drugs are proteins, they do not interact with other drugs in the liver or constrict blood vessels, considerations for patients taking other medications and one of the limiting aspects of triptans, the class of drug used to abort migraines considered a huge advancement when they were introduced in the 1990s.

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