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Migraine: stemming the tide of pain

Greg Weir

Greg Weir

Greg Weir, a PhD student at the MRC Functional Genomics Unit, explains why he’s turning to stem cells to investigate migraine in his shortlisted article for the Max Perutz Science Writing Award 2012.

What does migraine mean to you? Maybe it is only a mild inconvenience in your life, making a friend cancel on dinner or extra work for you as a colleague calls in sick … again. Or perhaps it means more to you. Perhaps it means hallucinatory visions followed by hours of pain that leave you bedridden and seeking sanctuary in the darkness. For me, it means something else as well. For me it means something frustrating, something exciting and a totally absorbing challenge. I’m a PhD student researching the causes of migraine.

The first thing I must do is convince you that migraine is worthy of research. No doubt this will be an easy task when it comes to the 18% of women and 6% of men who are themselves “migraineurs.” However, for those who do not suffer sporadic, intense headaches that can last several days, a hard financial fact might do the job. In theUSAalone migraine costs around $14 billion annually in direct medical costs and indirectly through lost work.

Migraine is not a new disease. Hippocrates described it in 400 B.C and before him the Egyptians treated it with clay crocodiles tied to the forehead. Even earlier, humans over 10,000 years ago were compelled to immortalise the migraine menace in their cave paintings. So given how much time we’ve known about the condition, why are we unable to effectively treat most migraine patients? We simply don’t know a lot about what is going on in the migraine brain.

There are two reasons why migraine is tricky to research. As usual, it’s at least partly in the genes. However it is not as simple as one faulty gene causing migraine. In fact we think that multiple genes interact with multiple different environmental factors to induce a migraine attack. Such complexity has meant that genes associated with migraine have not been easy to pinpoint.

The pain phase of a migraine is due to activation of the trigeminal nerve, which is responsible for sensing pain from the head and face. Therefore it makes sense to study the cells which make up this nerve in the laboratory. To do this cells currently have to be taken from rats or mice. This technique has ethical considerations but also means that experiments are being performed on animal cells which may act differently to their human counterparts.

As part of my PhD I am trying to create a model that takes into account both of these considerations. The aim is to generate disease-relevant cells outside of the body which can be used for basic research and drug screening. To do this I am using Induced Pluripotent Stem Cell (iPSC) technology. The term “stem cell” is likely to prick the conscience. However unlike embryonic stem cell research, iPSCs do not utilise embryos and instead are made from adult skin samples, rendering ethical issues minimal. The premise is to take skin cells from a patient and then genetically reprogram these into stem cells capable of turning into any cell type in the body, in my case cells akin to those found in the trigeminal nerve.

This is by no means a simple task, as it has never been done before. However with success would come great opportunities. As well as being the human version of the cell type we want to study, all cells will possess the genetic background of the original patient. This means I can look for differences between cells generated from migraine patients and cells taken from people who do not suffer from migraine. From here we can hopefully address the most fundamental of questions; in what way are migraineurs’ cells different, and crucially, why are they different? Such cells could also be used to screen drugs that might reverse observed differences. iPSC have significant advantages over traditional animal-based drug screening methods both in terms of relevance, due to the human origin of the cells, and ethics, as the need for animals is circumvented. All this is a large amount of blood sweat and tears away, but a goal I strive for nevertheless.

Migraine is scientifically fascinating in its complexity and the challenges this leads to when studying it. But fascinating is not enough. I want to make strides in our migraine knowledge that go beyond keeping lab folk like me fascinated, strides that drag us closer to therapeutic treatments. I might spend years with little success or my cells might, just might, help contribute in some way to drug advancement. Such a drug could be widely used or it might only help 0.01% of patients. Even in the latter scenario, that’s still hundreds of thousands of people experiencing less pain in their lives. Is migraine research worth doing? I’ll be heading to the lab first thing tomorrow morning …

Greg Weir

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