By Emily Burke, Ph.D., Director of Instruction,  |  Jun 5, 2019

First in Class Migraine Approval

Editor’s Note: June is National Migraine and Headache Awareness Month. Medical experts don’t fully understand what causes migraines, making the condition difficult to diagnose and treat. This week, Real World Health Care delves into the science behind migraine and its treatment, with this article written by Emily Burke of Biotech Primer. Next week, we’ll bring you insights from the perspective of a family caregiver supporting a loved one with chronic migraine.

Emily Burke, Biotech Primer

Emily Burke,

Migraine sufferers gained new hope last year when the FDA approved three new first-in-class drugs that prevent the onset of migraines, and significantly reduce the number of migraine days in difficult-to-treat (those that have failed 2 to 4 prior treatments) patient populations. In some patients dubbed “super responders,” migraine occurrence went from several times a month to no occurrence for six months. This is a big breakthrough that will have significant impact on the quality of life for migraine suffers who have not been able to find other forms of relief. Let’s take a look at the science behind migraines and how these new treatments work.

Attack of the Migraine

As many as 36 million Americans suffer from migraines—about 12 percent of the population. More than just a headache, migraines often include symptoms like intense pain, nausea, and extreme sensitivity to light or noise. They can last anywhere from a few hours to days on end. Episodes may be as frequent as several times a month, or as infrequent as a few times a year.

There are three distinct parts of a migraine episode; however, not all migraine sufferers experience these phases with the same intensity. Each set of symptoms is unique to the individual, and can include prodome, aura, or postdome phases.

  • Prodome occurs in the hours or days before a migraine attack. It includes mood disturbances, stiff muscles, and sensitivity to smells or noise.
  • Aura is the period just before the severe pain attacks. Visual distortions are the most common symptom, with sensory or motor disturbances potentially occurring as well.
  • Postdome happens after the actual headache and includes symptoms such as lingering pain and cognitive difficulties.

The Science Behind the Episode

While the exact cause is largely unknown, there are a few theories:

  • Brain Stem Changes: Research by the Mayo Clinic (Rochester, MN) suggests migraines derive from changes in the brain stem and its interaction with the trigeminal nerve. The trigeminal nerve supplies feeling to the face and is considered a pain-associated pathway in migraine attacks.
  • Lowered Serotonin Levels: Another area of active research involves the neurotransmitter serotonin. Serotonin is most often associated with mood—antidepressants known as serotonin reuptake inhibitors increase levels of serotonin in the brain. This neurotransmitter is also implicated in migraine pain pathways, with levels dropping during an attack.
  • Hormonal Link: Migraines are more common in women than men, so a hormonal link may be tied to the causality. There is often a reduction in symptoms after menopause.
  • Glutamate Accumulation: In recent years, a few gene variations that appear to increase the risk of developing migraines have been identified through genome-wide association studies. Two of these genes result in increased levels of the neurotransmitter glutamate, suggesting that accumulation of glutamate in synapses may be a trigger.

This Just In

The hot new kid on the block is calcitonin gene related peptide (CGRP) inhibitors. CGRP spikes during migraine attacks and is thought to play a role in the brain pathways that process pain. The exact molecular mechanism of how the CGRP spike is related to migraine onset is not yet fully understood, but CGRP is thought to sensitize nerves in the face, neck, and jaw, as well as alongside blood vessels surrounding the brain. A 2002 study provided strong evidence of a key role for CGRP in driving migraines. Injecting volunteers who were migraine-prone with the CGRP peptide induced a migraine within hours; injecting volunteers who were not migraine-prone resulted in a mild headache at worst. These studies helped to form the scientific basis for this new class of migraine drugs. The first approved, erenumab, is a monoclonal antibody (mAb) that blocks activation of the CGRP receptor. The antibody binds the receptor but does not activate it, and in so doing, prevents CGRP from activating the receptor.

Fremanezumab and galcanezumab, the other CGRPN inhibitors approved last year, are mAbs directed at CGRP itself. The idea is for the mAb to “mop up” CGRP before it reaches the receptor and triggers a migraine.

Cocktail Fodder: A Headache of the Past

We sometimes blame migraines on the stress of modern living. In some cases, stress is a trigger, but the headaches are hardly a modern phenomenon. Descriptions consistent with migraines are found in the ancient Egyptian medical text Ebers Papyrus, dating from 1550 B.C., as well as Hippocratic texts dating from 200 B.C.

About the Author

Dr. Emily Burke is the Director of Curriculum for Biotech Primer and is responsible for customizing client training, delivering training sessions and writing the Biotech Primer WEEKLY, a free electronic newsletter that explains the science behind the headlines. She received her B.S. in biological sciences from Carnegie Mellon University and her Ph.D. in molecular biology from the University of Southern Alabama.

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