Researchers from QUT have uncovered a biological mechanism behind the reduction in migraine frequency observed in chronic migraine sufferers after gradually discontinuing migraine medications.
This study sheds light on epigenetic changes within specific genes that play a role in transitioning from episodic migraines to chronic migraines.
Chronic migraine poses a significant challenge for approximately 2% of the general population. Overusing acute headache pain relief medications and other drugs can contribute to the development and persistence of chronic migraine.
Chronic migraine is defined by having headaches on 15 or more days per month for three or more months, with at least eight days meeting migraine criteria.
QUT geneticist Professor Divya Mehta and colleagues aimed to understand the process of migraine chronification, where migraine attacks become more frequent over time. Additionally, they explored how this process could be reversed.
The research team delved into longitudinal changes in DNA methylation, an epigenetic modification involving chemical “tags” added to DNA molecules in response to environmental factors, including therapeutic drugs. These tags can activate or deactivate genes.
DNA samples were collected from patients with chronic migraine before and after a 12-week withdrawal from medication treatment.
Patients maintained headache diaries, and responders (those with a greater than 50% reduction in monthly headache and migraine days) were compared to non-responders to identify DNA methylation changes associated with treatment response.
Key Findings
HDAC4 Gene: Epigenetic changes in the HDAC4 gene were linked to a reduction in headache days following medication withdrawal. Lower DNA methylation levels were associated with decreased headache days.
MARK3 Gene: DNA methylation within the MARK3 gene was linked to a reduction in migraine days. Lower DNA methylation levels in the MARK3 gene at the beginning of the study were associated with fewer monthly migraine days, serving as a predictive biomarker for treatment response.
These findings have significant clinical implications, suggesting that the HDAC4 and MARK3 genes could be potential therapeutic targets for migraine treatment.
Understanding the epigenetic changes related to medication withdrawal provides new insights into addressing chronic migraine and improving the quality of life for affected individuals.
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The research findings can be found in Clinical Epigenetics.
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