“Recently, we and research groups within the International Consortium for Cluster Headache Genetics network have identified a few key regions in our genome strongly linked to an increased risk of developing cluster headaches using GWAS. Genes in these regions could potentially represent future drug targets and we have begun to characterize one of the top candidates, MERTK, in patient and control tissue,” says Andrea Carmine Belin.
For the human studies, biological tissue from patients with a validated cluster headache diagnosis and neurologically healthy controls were collected.
As the researchers currently did not have access to human nervous tissue, they used rat tissue for studies of the trigeminal ganglion. For the animal studies, the rat trigeminal ganglion was dissected, and they studied MERKT, its ligands as well as receptors and ligands that are well known to be active in this tissue using immunohistochemistry.
Jacob Edvinsson and Lars Edvinsson, both at Lund University, took part in the study.
The next step
Primarily, the team plans to characterize MERTK and its ligands in other cell and tissue types from patients and controls and study how the activity is affected by immunological reactions in the trigeminal ganglion, as MERTK has an important role in neuroinflammation.
“We also want to examine MERTK in tissue from patients with headache diagnoses other than cluster headache to find out whether MERTK is affected specifically in cluster headache or is generally involved in other primary headaches such as migraine”, says Andrea Carmine Belin.
Cluster headache and migraines have some similar characteristics in terms of symptoms and are to some extent treated with the same type of medication.
The study was funded by the Mellby Gård Foundation and the Swedish Brain Foundation.
Publication
MERTK in the rat trigeminal system: a potential novel target for cluster headache?
Edvinsson JCA, Ran C, Olofsgård FJ, Steinberg A, Edvinsson L, Belin AC
J Headache Pain 2024 May;25(1):85