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A possible target for future treatment of primary headaches identified
Last reviewed: 02.07.2025
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Researchers from the Karolinska Institutet have identified an interesting potential therapeutic target for the treatment of primary headaches. They found increased amounts of a gene associated with cluster headaches, MERTK, and its ligand Gal-3 in the tissues of patients with cluster headaches. Their study is published in the Journal of Headache and Pain.
Elevated MERTK and Gal-3 levels
A genome-wide association study (GWAS) scans genetic markers across the genome and compares frequencies between patients and controls to identify genomic regions and candidate genes associated with a disease.
"We have made the first characterization of one of the genes most strongly associated with cluster headaches in a GWAS, the MERTK receptor, using our biobank of biological tissues from cluster headache patients and controls, as well as clinical data," says Caroline Rahn, a researcher in the same department and co-author of the study.
The researchers were able to show elevated levels of MERTK and the ligand that binds to MERTK, Gal-3, in blood samples from patients with cluster headaches compared to controls.
"The trigeminal ganglion is involved in pain signaling during headache attacks, and we were also able to localize both MERTK and Gal-3 to this region in rat tissue," says Felicia Jennisdotter Olofsgaard, a graduate student in Carmine Belin's research group and co-author of the study.
Potential treatment
These findings are important because cluster headache is a severe primary disorder for which available treatments are ineffective and associated with many side effects. In addition, there is currently no cure for cluster headaches, despite the fact that one in a thousand people suffer from the disorder.
"We and research groups within the International Cluster Headache Genetics Consortium have recently identified several key regions in our genome that are strongly associated with an increased risk of developing cluster headaches using GWAS. Genes in these regions may potentially be targets for future drugs, and we have begun to characterize one of the leading candidates, MERTK, in tissues from patients and controls," says Carmine Belin.
Next steps
First, the team plans to characterize MERTK and its ligands in other cell types and tissues from patients and controls and study how the activity of these components is altered by immunological responses in the trigeminal ganglion, as MERTK plays an important role in neuroinflammation.
"We also want to study MERTK in tissues from patients with other headache diagnoses to see if MERTK is specifically involved in cluster headaches or is generally involved in other primary headaches, such as migraine," says Carmine Belin.
Cluster headaches and migraines share some similar characteristics in terms of symptoms and are treated in part with the same types of medications.
Conclusion
The discovery of elevated levels of MERTK and its ligand Gal-3 in tissues of patients with cluster headaches opens up new avenues for the development of targeted therapies that could improve the treatment of these severe primary headaches. Further research will help to better understand the mechanisms of action of these genes and their role in different types of headache, potentially leading to new, more effective treatments.