New research from the University of California, San Francisco has identified a genetic mutation that is linked to migraines.
The mutation occurs in a gene called casein kinase I delta (CKIdelta), and the study’s senior investigator, Louis J. Ptacek, said this is the first time researchers have linked a genetic mutation to common migraines.
“It’s our initial glimpse into a black box that we don’t yet understand,” Ptacek, an investigator at the Howard Hughes Medical Institute at the University of California, San Francisco, said in a news release.
More than 30 million Americans suffer from migraines, and scientists don’t know what exactly causes them. Migraines are often characterized by intense, throbbing head pain, and are often accompanied by an aura, sensitivity to light and/or nausea.
The researchers discovered the gene by looking at the genetics of two families with a history of migraines. They noticed that a large portion of the migraine sufferers either had the mutated gene or had a parent who carried the mutated gene. In the lab, the researchers were able to show how the mutation affects production of the gene, which has many important functions throughout the brain and body.
“This tells us that the mutation has real biochemical consequences,” Ptacek added.
Scientists then looked at the effects of the mutated gene in a line of mice.
The mice who had the mutation had a significantly lower pain threshold for nitroglycerin-induced pain versus the mice who did not have the mutation.
Scientists also mimicked the sensation of a migraine aura in the mice using a technique called cortical spreading depression (CSD) – a wave of electrical ‘silence’ that follows electrical stimulation. Mice with the genetic mutation had less tolerance for this as well, which Ptacek said was “especially intriguing.”
Lastly, Ptacek’s team found that astrocytes, cells that are essential for neuronal functioning and health, in the brains of the genetically-mutated mice showed an increase in calcium-signaling, compared to the astrocytes in the brains of ‘normal’ mice.
“This is significant because we think astrocyte functioning is very, very relevant to migraine,” Ptacek said. “This is an enzyme, and so it modifies proteins. The question is, which protein or proteins does it modify that is relevant to migraine? How does it change astrocyte activity?”
All this research “puts us one step closer to understanding the molecular pathway to pain in migraine,” Ptacek said, adding this new information could help researchers devise better therapies for migraines.
Ptacek said he also believes there is more than one mutation associated with migraines – in fact, he thinks there are likely several – but this is the first to be discovered.
The study, published May 1 in Science Translational Medicine, was supported by funds from the National Institutes of Health, the A.P. Giannini Foundation, the U.S. Department of Defense, the Migraine Research Foundation and the Sandler Neurogenetic Fund.