Medicine Finnish large-scale study investigates the causes of migraines – Neurologist: “The first step towards personalized medicine”

The world’s largest mapping of migraine genes found 123 susceptible sites in the human genome. According to the researcher, the result is a first step towards individual medications.

Every sixth Finns regularly get migraine symptoms. The head hurts sharply, often one-sidedly. Lights and sounds interfere. Dizziness and vomiting.

One in three migraine patients has a so-called aura. It is a jagged phenomenon that vibrates in the field of view and usually lasts less than an hour. Aura disappears and then a severe one-sided headache begins.

Researchers have long debated whether aural and non-aural migraines are the same or a different disease and should therefore also be treated differently.

An international mapping of migraine genes led by researchers at the University of Helsinki seems to provide an answer.

Material is higher than in any previous similar study. There are 102,000 migraine patients and 770,000 healthy controls.

Divided into subtypes, there are approximately 15,000 patients with both aura and auricular migraines. IHGC Consortium databases.

The researchers found 123 genome sites where gene variation is different in migraine patients than in others. Previously, only 37 of these sites were known.

Carriers of mucosal and aura-free migraines were found to have essentially the same differences from healthy ones.

Exactly as defined by the criteria, three gene regions were associated with auricular migraine alone and two without aura, while nine together were associated with nine gene regions.

When the statistical accuracy is slightly reduced, it appears that most of the 123 gene regions found are associated with both auricular and non-auricular migraine.

“The general message is that auricular and non-auricular migraines are largely genetically similar,” says an assistant professor of statistics. Matti Pirinen Finnish Institute of Molecular Medicine Fimm. He led the research.

“This is a first step towards personalized medicine so that we can deduce from the genes which contraceptive drugs are best for each.”

Migraine patients a neurologist who has treated for more than thirty years Mikko Kallela considers the results to be sensible and practical.

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“Genetics seems to work the way we clinicians have thought. Mural and non-aura migraines have strongly the same basic tone and are treated in the same way. Most people do not have the plow left on, so there is no need to treat it, but they try to ease the headache, ”says Kallela.

“Of course, the study also highlighted the differences between aura-free and aura migraine. This is a first step towards personalized medicine, so that you can deduce from the genes which contraceptive drugs are best for everyone, ”says Kallela.

One the gene identified for auricular migraine regulates the calcium channels in nerve cells, or the transmission of a message from one nerve cell to another. The finding makes sense because the aura could be thought to be related to perceptual brain activity.

Of the other two gene regions associated with aural and two without aura migraines, it is not possible to guess how they affect. This is normal. The role of most genes in bodily function is not yet understood.

Gene mapping sheds light on another permanent issue in migraine research. It confirms the so-called neurovascular theory, i.e. the nervous system-vascular theory.

In migraines, the blood vessels in the brain dilate. This has been thought to be a source of pain and nausea. Either the blood vessels dilate to stretch the nerves or the blood vessels themselves hurt.

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It is also thought that when the brain tissue itself feels nothing, the pain must be vascular.

“Neither the central nervous system nor the blood vessels alone are enough to explain migraines.”

Since then, neurologists have pointed out that vision problems can hardly be caused by blood vessels and that the brain can produce pain sensations, even if they don’t actually “happen to them”. According to this school, the cause of the pain would be nervous.

Here among the risk factors for migraine, genes affecting both the nervous system and blood vessels were found in the gene mapping.

“The finding would reinforce neurovascular theory. Neither the central nervous system nor the blood vessels alone are enough to explain migraines, ”said a dissertation researcher working on genetic mapping and the first author of the article. Heidi Hautakangas Says about Fimm.

The study was published in a respected scientific journal Nature Genetics.

Gene is the part of the genome that contains the code for building a particular protein. This is the basis for the connection and development of drugs, genes and proteins.

First, genetic mapping can be done. If migraines have a particular gene form more often than others, then that gene form can cause migraines. In this case, drugs can be developed that attach to the protein or receptor produced by that gene and render it ineffective or act on the protein or receptor in some other way.

Or you can try a wide variety of medications and see if they happen to help. The exact mechanism why drugs help will only become clear later.

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However, the mechanisms of action of triptans and new biological inhibitors developed as specific migraine drugs are well known. Two of the areas found in the genetic mapping of Hautakangas and Pirinen are well-suited to these drug research findings.

First is a gene encoding the serotonin 1f receptor.

“Serotonin is a neurotransmitter that relieves pain by going to certain receptors. In the past, it has been found that triptans cleave to serotonin receptors 1b and 1d and 1f, thus relieving pain, ”explains clinician Kallela.

“A lasmiditan drug that only affects the 1f receptor has recently been developed. Here, therefore, gene mapping hit the same area as drug developers, which, of course, increases the credibility of moving in an area that is important for migraines. ”

Another gene region relevant to drug discovery encodes the production of the cgrp mediator.

Cgrp is a small protein that produces pain and dilates blood vessels. During a migraine attack, blood cgrp levels are elevated.

The effectiveness of biological inhibitors is based on the inhibition of cgrp. Drugs either adhere to the cgrp molecule or fuse to block the receptor to which cgrp should go.

Could you to develop new drugs using the new gene regions now discovered?

“Our genetic mapping is looking for computational connections between genes and symptoms. The mechanisms of action must be investigated separately in the laboratory. However, ideas for new drug target molecules can be found in gene mapping. Therefore, in the future, it is necessary to map migraine genes with even larger data, ”says Pirinen, who led the research.

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