NCNK 81 TRESK Gene Implicated in Migraine

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KCNK 18 TRESK Gene Implicated in Migraine

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For some time, researchers have been diligently working to identify the genes responsible for Migraines. The first identified are associated with hemiplegic Migraines.

Now, researchers have identified a gene mutation that could impact triggering Migraines and provide a direction for developing new treatments.

Using DNA samples from multiple generations of a large family with Migraine with aura, the researchers were able to identify the mutation on a gene known as KCNK18 or TRESK that was common to the members of the family. It's believed that this mutation alters the electrical activity in certain brain cells. When this gene doesn't work as it should, Migraine triggers can more easily bring on a Migraine attack. The study's lead author, Ron Lafreniere, said,

"When we tested everyone in the family, all those who suffered from migraines also had the mutation."³

The mutation of the KCNK18 gene interferes with the production of a protein called TRESK. TRESK is important in regulating the sensitivity threshold of the brain's pain centers. Dr. Zameel Cader, one of the researchers, said that Migraines "seem to depend on how excitable our nerves are in specific parts of the brain."³

More comments from Dr. Zameel Cader, University of Oxford:

"Previous studies have identified parts of our DNA that increase the risk in the general population, but have not found genes which can be directly responsible for common migraine...

What we've found is that migraines seem to depend on how excitable our nerves are in specific parts of the brain...

Finding the key player which controls this excitability will give us a real opportunity to find a new way to fight migraines and improve the quality of life for those suffering...

So what we want to do is find a drug that will activate the gene."⁴

From Migraine expert and researcher Dr. Peter J. Goadsby:

"The identification of a mutation in a gene for the potassium channel in a family with migraine with aura provides both a further important part of the puzzle in understanding the biology of migraine, and a novel direction to consider new therapies in this very disabling condition"⁴

Summary and comments:

TRESK impacts the K2P (potassium) channels through out the nervous system. The K2P channels play a key role in the excitability of neurons in the brain. They're also a target for many anesthetics and neuroprotective agents and have been implicated in several pain pathways in the brain.¹ This may provide a lead to developing new treatments and may be a clue to why some medications now in use for Migraine prevention work for some Migraineurs.

This is a very important scientific discovery with the potential for better understanding of Migraine cause and pathophysiology as well as the development of new treatments. While it is definitely an encouraging discovery, the excitement should be tempered with patience because the journey from this discovery to new treatments will not occur quickly.

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Resources:

¹ Lafrenière, Ronald G; Cader, M Zameel; Poulin, Jean-François; Andres-Enguix, Isabelle; Simoneau, Maryse; Gupta, Namrata; Boisvert, Karine; Lafrenière, François; McLaughlan, Shannon; Dubé, Marie-Pierre; Marcinkiewicz, Martin M; Ramagopalan, Sreeram; Ansorge, Olaf; Brais, Bernard; Sequeiros, Jorge; Pereira-Monteiro, Jose Maria; Griffiths, Lyn R; Tucker, Stephen J; Ebers, George; Rouleau1, Guy A. "A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura." Nature Medicine. September, 2010. doi:10.1038/nm.2216

² Science News. Health and Medicine. Gene Linked to Common Form of Migraine Discovered. Science Daily. September, 27, 2010.

³ Staff Reporter. "Migraines: Blame your mother?" The Week: Health and Science. September 29, 2010.

⁴ Staff Reporter. "Migraine cause 'identified' as gene defect." BBC News: Health. September 27, 2010.

Medical review by John Claude Krusz, PhD, MD

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