Approved Research

Migraine classification, mechanism, and comorbidities

Lay summary

Migraine is a severe and unique form of headache and a leading cause of disability worldwide.  Up to 15% of the population experiences migraine, with rates 2-3 higher among women than men.  Formally codified symptoms are used in diagnosis of migraine and its classic subtypes, migraine with (MA) and without (MO) aura.  Although new migraine medications have been introduced recently, available treatments remain at least partially ineffective or even contraindicated for many. Major urgent issues in improving care for migraine are 1) developing quantitative measures rather than currently used qualitative symptom-based criteria to improve diagnosis of migraine; 2) elucidating causal mechanisms of migraine pathophysiology to identify new therapeutic strategies; and 3) understanding the basis of migraine comorbidities, which include a clinically important ~2-fold increased risk of ischemic stroke as well as gastrointestinal complications.

The current proposal has potential to address all three issues.  The initial aim of the proposed research is to develop a plasma-based (i.e. blood-based) biomarker signature that would provide a quantitative measure of the susceptibility to migraine attack that could be used to complement the current symptom-based approach to diagnosis.  A second aim would assess whether any biomarker associations may reflect causes of migraine that may elucidate the pathophysiology that underlies migraine or could be targeted in development of new therapeutics.  The third aim would investigate the relationship between any biomarkers related to migraine and migraine comorbidities.

There are many potential impacts on public health.  If the proposed biomarker signature can be developed, it would be useful for diagnosing susceptibility to migraine attack in a quantitative way, potentially providing objective measures of migraine severity and migraine subtype that could help optimize choice of treatment via future clinical trials.  Beyond the precision medicine goal of optimally matching patients to treatments, a plasma biomarker signature of migraine attack susceptibility may also have value as a quantitative readout of the effect of various treatments in future clinical trials.  Within the biomarker signature, any proteins or metabolites that appear to cause migraine as judged by findings from the proposed genetic analysis, would provide clues for the development of new therapeutics as has been done for other clinical conditions.  Similarly, insights into the causal biology by migraine may help offset the impact of its comorbidities, particularly ischemic stroke.  The project is expected to require up to 3 years to complete.