Possible target for future treatment of primary headaches identified

Researchers from the Karolinska Institute have identified an interesting potential therapeutic target for the treatment of primary headaches. They found increased amounts of the cluster headache-associated gene MERTK and its ligand Gal-3 in tissue from patients with cluster headaches. Their research was published in the Journal of Headache and Pain.

Elevated levels of MERTK and Gal-3

Genomic association studies (GWAS) scan genetic markers across the genome and compare frequencies between patients and controls to identify genomic regions and candidate genes associated with disease.

"We made the first characterization of one of the genes most strongly associated with cluster headaches in GWAS, the MERTK receptor, using our biobank of biological tissue from cluster headache patients and controls, as well as clinical data," says Caroline Ran, a researcher in the same department and co-author of the study.

Researchers were able to show increased 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 Olofsgård, a graduate student in Carmine Belin's research group and co-author of the study..

Potential treatment

These results are important because cluster headache is a severe primary disorder for which available treatments are limited in effectiveness and are associated with many side effects. Additionally, there is currently no cure for cluster headaches, despite the condition affecting one in a thousand people.

"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 could potentially be targets for future drugs, and we have begun to characterize one of the lead 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 to 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 involved in other primary headaches such as migraines," says Carmine Belin.

Cluster headaches and migraines share some similarities in terms of symptoms and are partly treated with the same types of medications.

Conclusion

The discovery of elevated levels of MERTK and its ligand Gal-3 in the tissues of patients with cluster headaches opens up new prospects 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, which could potentially lead to new, more effective treatments.