Migraine Pathophysiology and Treatment Advances

Understanding the genetic underpinnings of the disease is really key to developing new drug targets and new therapies. Right now we have at least four autosomal dominant genes that have been identified to account for at least some of the rarest subtypes of migraine, and some genome-wide association studies have identified at least a dozen variants that increase the susceptibility to disease. All of those genetic mutations and all of these genetic variants if you will, all seem to point to a singular problem in the brain which is one of hyperexcitability. So certain networks within the brain become hyperexcitable and that accounts for not only the pain but other neurological and vegetative and systemic symptoms that come along with migraine.

Over the past two decades, we have had a single drug class that’s been introduced for the acute treatment of migraine. That happens to be the only drug class that’s been approved for migraine in the past 60 years. We’ve not made a tremendous amount of therapeutic gains but that single class has really ushered in a new era of understanding of the molecular pharmacology and receptor targets for migraine. That has opened up a plethora of new targets for drug discovery. Right now, while we’ve moved from the blood vessel to the space between the blood vessel and the nerve to the brain, we are now focused on molecular targets in the brain rather than the blood vessel. This era of receptor pharmacology where we’re targeting the brain is really exciting. We’ve got at least a dozen new chemical entities that are in various phases of clinical trials for the acute and for the preventative treatment of migraine.

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