Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
How many people are thought to suffer from migraines and in what way does migraine severity vary?
Migraine affects an estimated 30 million people in the U.S, with the one year prevalence of migraine estimated at 12% of the general population, including 18% of all women and 6% of all men.
What is adiponectin (ADP) and where is it found?
Adiponectin is a protein that functions much like a hormone with roles in cardiovascular disease, metabolism, lipid and glucose metabolism, reproduction, as well as immune and inflammatory roles. It is predominantly produced by fat cells.
How did your research into ADP and migraine severity originate?
My earlier research evaluating the epidemiological association between migraine and obesity demonstrated that the risk of migraine and severe headaches was increased by about 38-39% in those with obesity. In addition in the mid 1990s the scientific community’s awareness that adipose tissue is not just a storage depot for fat began to increase.
It is now well established that adipose tissue plays important roles in multiple biological processes other than storing fat. This includes roles in reproduction, metabolism, and importantly, in immunity and inflammation.
Adiponectin was one of the early proteins recognized to be secreted from fat cells and to play a role in inflammation. It was also shown to modulated some of the inflammatory proteins already implicated in the neurogenic inflammation of migraine.
Why is there a need to identify a biomarker for migraine that predicts treatment response?
Currently migraine diagnosis, prognosis, and treatment response are determined based on clinical history and symptomatology that the patient discusses with their doctor.
There is no operational migraine biomarker to objectively identify migraine. This also limits our ability to predict risk of progression and response to treatment without waiting to see how someone does or does not respond to a particular treatment.
The official NIH definition of a biomarker is: “a characteristic that is objectively measure and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”
Biomarkers can serve in multiple ways. For example they may be useful as an indication of the probable effect of treatment on patient (e.g. predictive biomarkers), or to identify the presence of a disease that already exists (e.g. diagnostic biomarker) or how such a disease may develop in an individual case regardless of the type of treatment (prognostic biomarker).
Predictive biomarkers help to assess the most likely response to a particular treatment type, while prognostic markers shows the presence or progression of disease with or without treatment. In contrast, drug-related biomarkers indicate whether a drug will be effective in a specific patient and how the patient’s body will likely react to it.
What did your research involve?
In this study, 20 women migraine sufferers presented to our clinic during an acute migraine attack. We took their blood before and after acute abortive treatment with sumatriptan/naproxen sodium (suma/nap) versus placebo and evaluated blood levels of the total protein adiponectin and the fragments it is composed of which circulate in the blood.
The fragments have different functions. The largest fraction called HMW adiponectin is predominantly proinflammatory. The smaller fragment called LMW adiponectin is predominantly anti-inflammatory.
We then looked to see how the study participants pain ratings correlated to the total and fragments of adiponectin – ie we evaluated how adiponectin and its fragments correlated to pain severity.
We then also looked to see how these levels correlated with treatment response and if based on these levels at onset we could predict who would respond to the study treatment at 2 hrs after treatment.
What did your research find?
In this pilot study of women episodic migraineurs, we found that the ratio of the proinflammatory fragment –HMW adiponectin to the anti-inflammatory fragment :LMW adiponectin ratio was associated with migraine severity.
For every 1 point increase in the HMW:LMW adiponectin ratio, pain increased by 0.22. Additionally based on the HMW:LMW ratio levels at the onset of pain, we could predict who would get pain-relief or be responders to study treatment at two hours.
What impact do you think your research will have?
This study is exciting in that it represents a first step in identifying a potential predictive and response biomarker for migraine. If this data can be replicated and confirmed there is potential for the HMW:LMW adiponectin ratio to be an operational and useful biomarker for identifying migraine and monitoring and predicting treatment response.
This could help us to guide our treatment choices for migraine patients more effectively and even potentially lead to new therapies. However it is still too early to know for sure and more research is still needed.
How do you think the future of migraine treatments will develop?
Given how common migraine is and the increasing awareness of the substantial personal and societal burden migraine can have on healthcare, I think the interest and our ability to develop better and more effective treatments and treatment strategies will only increase.
However this necessitates patients and physicians working together to do solid and novel research directed to this goal, as well as the support and funding for headache research from both public and private sources.
Where can readers find more information?
There are several great internet resources for women. Two sites I encourage my patients to check out are the American Headache Society and the International Headache Society web pages for more information on migraine and other headache disorders.
About Dr. B. Lee Peterlin
Dr. B. Lee Peterlin is an Associate Professor in Neurology and the Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore, MD.
Her research interest has focused on factors that influence the onset and progression of migraine headaches. In particular Dr. Peterlin’s work focuses on the impact of hypothalamically mediated comorbidities, such as obesity, on migraine and the mechanisms for such associations.
She was awarded the 2009 National Headache Foundation lectureship for her work in regards to the association between obesity and migraine.
She is a member of both the American and International Headache Societies (AHS/IHS), as of the American Academy of Neurology’s Headache & Facial Pain Working Group.
She has published numerous articles on headache, written several book chapters on headache, co-edited a handbook for primary care physicians on menstrually-related migraine and is an associate editor for the journal “Headache”.