Migraine Genetics – What if…?

We’ve been talking about migraine genetics for many years now. There have been a number of exciting developments, including the report this past June of a huge study of almost 60,000 migraine sufferers.

Many of us would like to think of genetics as a (small) series of on/off switches. This gene causes migraine. Please turn it off.

But here’s a different way to think about migraine genetics – maybe you’ll find it helpful.

Instead of thinking of migraine as a disease, like cancer or a bacterial infection, think of it as something “natural” that could happen to everyone (not normal – bear with me). Another example of something “natural” that could happen to anyone is that they could fall down. It’s a gravity thing.

So think of a building with a foundation. You are that building.

Your genetics provide the foundation, keeping the building from collapsing (into a migraine attack, or lifelong migraine attacks).

Now there are all types of foundations. They work well for different types of buildings. Normally, that’s just fine – we’re all individuals and have a different genetic makeup, and that’s the way it’s supposed to be.

So some people may be more susceptible to migraine than others, but normally none of us should ever get sick, or have a migraine attack.

But things can actually go wrong with this wonderful genetic balance. There may be several bricks in the foundation with cracks, or there may be missing bricks. If you have several of these problems, the risk of the collapse increases (your risk of migraine increases). There can also be outside, non-genetic factors that could trigger the actual collapse in a building with a weak foundation, like a car driving into the building (yes, that does happen in real life).

There are also key parts of the foundation that simply have to be in good condition. Maybe a column, or cornerstone. If there’s a genetic problem in certain places, you are guaranteed to have migraine (this is called a “causal gene” – it may not be the only factor, but if you’ve got this genetic problem you have migraine – period.).

Now, as you can see (and as you’ve experienced if you’ve ever dealt with problems with foundations), it’s not a matter of just replacing a brick, or switching a switch. There are multiple factors involved.

In her interview at the recent World Migraine Summit, Professor Lyn Griffiths listed three categories of genes that seem to be involved when it comes to migraine – neurotransmitter related, hormone related, and vascular related. Different problems with call for different solutions.

The recent study identified 38 independent genomic regions that were related to migraine. Interestingly, a large number of the new relationships discovered were also related to vascular health (blood vessels).

Now, we’ve discovered that we have some cracks in the foundation. What do we do?

First, we could actually try to “repair” the genes. There are actually technologies, such as CRISPR, which allow us to actually “edit” DNA, and that means that the changes would be passed on to the next generation.

Playing with fire? Considering how complex DNA is, and how many other factors interact with it, you bet. But if an edit could cure an inherited disease, by “flipping a switch”, why not do it?

We won’t get into that controversy today. But the fact is that migraine tends to be very complex genetically – we have a lot still to learn. And there is more than one way to stop migraine in its tracks.

I asked Professor Griffiths about technologies like CRISPR, and her response was interesting:

Regarding the use of CRISPR and similar technologies in the treatment of conditions like migraine, I’m pleased about the capacity for us to research the effects of gene mutations and even polymorphisms with a precision that we could never achieve before. CRISPR offers us the capability of altering cell lines and then comparing the effect of these genetic changes while leaving the background of a cell unchanged and undistorted by viral vectors.

The capacity to use this for advanced pharmacogenetic research to develop personalised treatment response profiles is significant. It also allows us to potentially take into account gene-gene interactions in our analysis allowing us to edit common polymorphisms in gene pathways to see how contributing genetic variations add to the potential for migraine in individuals.

You don’t need to follow all the technical language to see the point. Maybe CRISPR isn’t going to do a simple “edit” in the near future to cure your migraine. BUT, what if it could further research by telling you which migraine symptoms were affected by which genetic factors? What if it could give you tips on how to either repair the foundation, or place additional supports where they’re needed?

We need to move past this idea that migraine is migraine and we need a pill that everyone can take to cure it. The reality is that there are many types of migraine, each one with its own genetic signature and its own symptoms.

What if you could get a DNA test, and that test would tell you which type of migraine you had?

Maybe a genetic problem could be repaired. But more likely, an extra support could be added to the foundation.

Let’s say this set of genetic factors leads to the specific type of migraine you have – because the factors cause a drop in a certain vitamin in your system. A simple vitamin supplement could completely erase your migraine attacks. Or – yes – even a custom medication. Or maybe even a certain exercise.

It may be quite a few years before this kind of customized treatment is a reality. But there is great hope that a “cure” – that is, the ability to erase many subtypes of migraine – may be very possible, and may be available to our children, if not to us.

Meanwhile, we don’t have to wait for that long before genetic research will help us. Migraine genetic research may not be ready to give us the final answer for every type of migraine, but it is giving us clues into the directions we need to go for treatment.

We are learning that these genetic factors indicate that certain supplements may help, or that certain drugs need to be researched. That may not be the customized treatment we want, but it is actually helping people with migraine right now.

If you would like to learn more about the work of Professor Lyn Griffiths and her team, visit the Genomics Research Centre. I hear they’re looking for migraine patients who are willing to share their DNA.

Also, did you know that Professor Griffiths’ research is supported by the Migraine Research Foundation? Use the links on the sidebar to give a few dollars to the MRF to help keep this research moving forward! (Or, visit our community page to help today!)