Migraine Breakthrough Gives Sufferers Hope (Study Points to Cause of Migraines)

[Turborama]

Source: Sky News

4:02pm UK, Monday September 27, 2010 -

Kat Higgins and Osman Baig, Sky News Online -

Scientists have identified a faulty gene responsible for causing the debilitating headaches associated with migraines.

The finding could offer new hope to sufferers and lead to better treatment for the one in five people who have the neurological disorder.

Researchers at the University of Oxford, along with colleagues in Canada, used DNA from people who experience migraines and their families. They found that when a gene called Tresk is defective it can trigger pain nerves in the brain causing a severe headache.

The discovery could lead to the production of a new drug that can switch off the pain and consequently greatly improve a sufferer's quality of life.

Read more: http://news.sky.com/skynews/Home/UK-News/Migraines-Oxford-University-Discovers-Faulty-Gene-Tresk-That-Leads-To-Debilitating-Headaches/Article/201009415745474?lpos=UK_News_First_Home_Article_Teaser_Region_4&lid=ARTICLE_15745474_Migraines:_Oxford_Unive

---

Study points to cause of migraine

Source: Britain's NHS - Behind the Headlines

Scientists have discovered how to switch off the pain of migraines, The Daily Telegraph reported. The newspaper said that new drugs may soon be able to counteract the debilitating headaches.

The study behind the news analysed the DNA of over 1,200 people to look for mutations within a gene known to play a role in the working of nerve cells. The analysis found a particular mutation in a woman who had migraines with “aura” (visual disturbances that accompany a migraine). When the mutation was traced back through the woman’s family, it was found that all those who carried the mutation also had migraines with aura. Further testing of the mutation showed that it affects the way cells in the spinal cord and brain chemically transfer signals to each other.

As yet, we do not know how commonly people with migraine and aura are affected by the mutation, or whether mutations in the gene might play a role in migraine without aura. Also, there are likely to be a variety of genetic and environmental risk factors that increase the risk of getting migraines. While this genetic discovery may eventually help migraine sufferers, the media have over-interpreted this research as it is too soon to anticipate that it will lead directly to a treatment.

Where did the story come from?

The study was carried out by researchers from Université de Montréal in Canada and other research organisations across the world. It was funded by Genome Canada, Genome Quebec, Emerillon Therapeutics, the Wellcome Trust and the Pfizer pharmaceutical company. It was published in the peer-reviewed medical journal Nature Medicine.

This genetic study is an important but early step in the investigation of potential genetic causes of typical migraines with aura. It is unclear whether it will have an application for migraine treatments and it is too soon to claim that scientists have discovered how to “switch off” the pain of migraines. This study did not investigate a treatment.

Much more: http://www.nhs.uk/news/2010/09September/Pages/genetic-mutation-cause-of-migraine.aspx

Links to the headlines

http://www.telegraph.co.uk/health/healthnews/8026075/Scientists-discover-how-to-switch-off-pain-of-migraines.html">Scientists discover how to 'switch off' pain of migraines. The Daily Telegraph, September 27 2010

http://www.bbc.co.uk/news/health-11408113">Migraine cause 'identified' as genetic defect. BBC News, September 27 2010

http://www.express.co.uk/posts/view/201954/Hope-for-9-million-migrane-sufferers">Hope for 9 million migrane sufferers. Daily Express, September 27 2010

Links to the science

Lafrenière RG, Cader MZ, Poulin JF et al. http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2216.html">A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura. Nature Medicine, (Published online) September 26 2010

http://www.nhs.uk/Pages/HomePage.aspx">

http://www.nhs.uk/aboutNHSChoices/aboutnhschoices/Aboutus/Pages/the-information-standard.aspx">

[BrklynLiberal]

1. I hope treatment is next on their agenda

Imitrex is fantastic for relief, and topamax is pretty good for prevention...but the side effects can be problematic.

[HillWilliam]

4. Topamax and gabapentin

are working pretty well for prevention, but I still have to resort to some hefty stuff once in a while. I sure wish Imitrex worked for me. That works pretty well for my partner, but nothing much seems to budge my migraines when they finally hit. On the up-side, with topamax and gabapentin, I've gone from 3-4 a month to 3-4 a year. I call that a resounding success.

Oh, for the day when I wouldn't have to put up with the damned things at all (wistful sigh)

[BrklynLiberal]

9. I am with you on that...

[Mz Pip]

2. Mutated genes.

Kind of weird to learn that I have mutated genes floating around in me.

Fortunately, I don't seem tofhave any negative side effects from Imitrex or Maxalt but it would be nice if that mutated gene could just be turned off and I wouldn't have to take the pills at all.

[AngryAmish]

10. I hate to break this to you, but all of our genetic code is mutations

It is how natural selection works.

[Mz Pip]

15. Yeah

I kind of know that. Still I feel weird about carrying around genes that should be naturally selected out of the gene pool. Having migraines does not advance our species in anyway that I can think of.

I can't run from predators with a migraine. I can't solve a quadratic equasion either. Can't do anything of any value whatsoever.

[Duer 157099]

18. Well... let's look at the other side

If it were such a liability, the mutation would have disappeared by now. Clearly, it offers some sort of advantage.

Just one aspect to think about: if you get the aura, look around at the art world, especially ancient. You'll notice that images that look startlingly similar to a migraine aura is depicted in art the world over. Also, I would guess that people who "saw" strange shapes and lights were probably likely to be designated the village shaman or medicine man or equivalent. Perhaps suffering from migraines makes one more sympathetic to others' pain? I can think of lots of genetic advantages to this horrible curse, lol.

Gotta look for the silver lining, right? :D

[unblock]

20. natural selection is based on passing genes on to your progeny

something only gets selected out if it hinders this. migraines don't hinder survival prior to breeding age (aside from perhaps a very small number of suicides or lethal medical mishaps) nor do they interfere, as far as anyone knows, with mate selection and breeding.

there are plenty of features that don't offer any particular "advantage" but natural selection doesn't care unless it has something to do with survival and ability to procreate.

[AngryAmish]

19. Maybe the genes are needed for consciousness, or keep our hearts beating

or a million other things. Sickle cell-type is an example. One version of this gives some immunity from malaria. Two of these genes = sickle cell. (I think. I'm not a geneticist.)

A really interesting commonish mutation is tay-sachs type. Ashkenazi Jews, on average, have IQs higher (7-11 points) than the average American. There is some suggestion that having one set of tay-sachs marker confers an intelligence advantage. Interesting theory, no?

[mike_c]

25. a better term is simply "allele"-- mutation carries too much negative connotation...

...while "allele" just means a different version of the same gene. Never mind that mutation is how it got that way. As for whether your version of that gene is maladaptive, it really isn't unless it interferes with your reproductive fitness. Arguably, people who spend all day lying on their backs moaning in a darkened room with their eyes tightly closed are MORE likely to reproduce than women who are actually aware of what their partners are doing, smell like, and so on.... :rofl:

[kenichol]

26. My green eyes are a mutation

I remember when my blue-eyed daughter learned that in school & couldn't wait to share that bit of science with me when she got home.

[Politicalboi]

3. I had a friend who's father was a

Fire fighter, and when he saw the "flash" he took an Alka Seltzer and it worked for him. I'm only posting this to maybe help someone who gets migraines. I hope it works for others as I hope this new drug does too.

[crazylikafox]

5. My mother takes an aspirin as soon as she sees "the lights"

This seems to work for her. I think Alka Seltzer contains aspirin also.
Luckily for me, these headaches passed from my Grandmother to my mother to my sister, but not too me.

[Duer 157099]

7. Lucky indeed! You had a 50% chance of getting it

I was the unlucky 50%, as is my son. And sister. We should volunteer for one of these studies, I'd love to know what mutation we have.

[Turborama]

12. I didn't know about the 50% chance. My mother and brother suffer from them & I don't

Do you know if I carry the potential to pass it on even if I don't suffer from them? The reason I ask is that my wife gets them and I'm wondering if my family history affects those 50% odds.

[Duer 157099]

13. It's a dominant gene, so only one copy will result in getting migraines

(although since not all info is yet known about the genetic aspects of this, the info might change if they find that a second or third gene are also involved)

But at least for the mutation they are discussing in that article, it's dominant, so if you have one copy, you get migraines. If you don't get migraines, you don't have that mutation.

[unblock]

21. i consider myself lucky i DID get the migraines

i got the x chromosome with migraine instead of the x chromosome with bipolar disorder instead.

my brother got that.

[crazylikafox]

27. Interesting, because my son gets them.

Even though I don't. If it's a dominant gene, and I don't have it, then how did I pass it on? I'm wondering if his are not true migraines, just major headaches caused by stress or other factors, such as poor diet.

[Duer 157099]

29. Lots of possibilities

Perhaps you have the mutant gene, but you ALSO have another mutant gene that offsets/overcompensates for the first mutation?

Or, perhaps your son mutated the gene all by his lonesome, a budding molecular geneticist with innante talent?

Or, there are several different mutations of the same gene and they vary in how they predispose one to migraines?

Lots of possibilities, especially in a field that still has more questions than answers.

But good question! :thumbsup:

[Duer 157099]

6. I'll try that next time

It makes sense, because the mutant protein they are talking about is sensitive to changes in pH (well, I suppose most proteins are...)

I'm one of those who gets the aura, so this is fascinating to me. I've never even heard about this gene or protein.

[thecrow]

8. I get the "flash" but no headache

I used to get terrible headaches until my doctor put me on a regimen of Elavil years ago.

Now I only get the visuals which can be debilitating or even dangerous if I'm driving.

I'm hoping they can find out what causes this and fix it.

[Duer 157099]

11. Thanks for posting this, that was actually a good article

Usually these kinds of articles are really vague, but this one went into sufficient depth.

I found a source of even more in-depth info here:

http://www.wipo.int/pctdb/ja/wo.jsp?WO=2008058399&IA=CA2007002084&DISPLAY=DESC

for the uber geeks.

What's absolutely fascinating, to me, is that this one genetic mutation (F139WfsX24) causes the EXACT SAME AURA in all of the family members!! To me, that is simply astonishing. The aura has been, to me, the most mysterious aspect of migraines and I've tried to understand what actually is happening (besides the cortical spreading depression). From that link above:

Furthermore, all affected individuals in this pedigree had the same type of aura with black spot scotoma, suggesting genetic homogeneity. Also, the trait was inherited in a dominant fashion, and seemed to be fully penetrant, suggesting that this mutation acts in a dominant negative manner.

And then there is this:

Nat Neurosci. 2008 Jul;11(7): 772-9. Epub 2008 Jun 22.
Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels.

Bautista DM, Sigal YM, Milstein AD, Garrison JL, Zorn JA, Tsuruda PR, Nicoll RA, Julius D.

Department of Physiology, University of California, San Francisco, 600 16th St., San Francisco, California 94143-2140, USA.
Abstract

In traditional folk medicine, Xanthoxylum plants are referred to as 'toothache trees' because their anesthetic or counter-irritant properties render them useful in the treatment of pain. Psychophysical studies have identified hydroxy-alpha-sanshool as the compound most responsible for the unique tingling and buzzing sensations produced by Szechuan peppercorns or other Xanthoxylum preparations. Although it is generally agreed that sanshool elicits its effects by activating somatosensory neurons, the underlying cellular and molecular mechanisms remain a matter of debate. Here we show that hydroxy-alpha-sanshool excites two types of sensory neurons, including small-diameter unmyelinated cells that respond to capsaicin (but not mustard oil) as well as large-diameter myelinated neurons that express the neurotrophin receptor TrkC. We found that hydroxy-alpha-sanshool excites neurons through a unique mechanism involving inhibition of pH- and anesthetic-sensitive two-pore potassium channels (KCNK3, KCNK9 and KCNK18), providing a framework for understanding the unique and complex psychophysical sensations associated with the Szechuan pepper experience.

I'm not sure whether this would suggest that peppercorns might actually *trigger* a migraine, or could be used against them, but they are certainly working at the same protein that is directly involved in migraines.

Awesome info, thanks for posting! :thumbsup:

[Turborama]

16. You're most welcome

I'm really glad you found it useful.

Thank you for your additional information, that fact about the exact same auras being passed on is fascinating.

:hi:

[gkhouston]

35. Thanks. I'd forgotten about the visual auras. It's been so many years since I

had a full-fledged migraine (I'm on topamax) but yes, I remember the auras. Never realized I might be having the same ones my dad had!

[madokie]

14. I have the aura of migraines

only had the pain part three times in my 62 years and let me tell you that is the most excruciating pain I've ever felt. All three times it put me to bed for days. The aura that I get is only a light show and usually last from a few minutes to a half hour or so. These started back when I was just a kid and I never knew what they were until I finally talked to a doctor after having one of those migraines that put me to bed.

[Mz Pip]

17. I had the aura migraines

as a teenager. No pain, I just couldn't see very well though the auras. Then I progressed on to cluster headaches. Worst. Pain. Ever.

Now I just get regular migraines, no aura and not of the cluster variety. I was hoping to outgrow these damn things but no luck.

[madokie]

28. I feel for you

I had an accident that took my inner ear out and upon returning home from the operation I had the last (so far) migraine. It was the migraine where I was able to find out that the pain I was feeling was a migraine and not a symptom from my surgery which I thought at first. My first migraine was a ten day affair as I didn't know what the deal was and so I kept on working right through it. This was the summer I graduated from HS and right before I was drafted. When I got into the Navy they kept asking us is anyone here ever had a migraine and me not knowing what I had that I had gone through at the time never told them. Lucky for me as they would have given me a medical discharge if I had told them.

My first experience was when I was working during the summer between the 9th and 10th grade and on the way to work I got tunnel vision and that lasted for most of the way to work, 50 or so miles, then it just quit then about mid morning as I was working in a closet, we were hanging drywall, it was like someone had closed the door opening on me so I just set down thinking one of the guys I was working with had done just that but then after a little bit I felt and there was nothing in the door then I realized I had gone completely blind. that lasted for about 30 minutes or so before I started to be able to see again. Neither the tunnel vision or the blindness has occurred again. At the time I was working all day and then staying out most of the night with my girlfriend and not eating right so I figured that was the cause.


does smoking pot help with the headaches any? I know that the last migraine I had out of desperation I smoked a bowl of weed and it seemed to help or it put me in a better mood maybe.

[Duer 157099]

30. Yes, migraines does happen to be one of the indications for medical cannabis

Some people claim it does the opposite for them, but the last migraine I started to get, I tested my theory and I'm one of the lucky ones for whom cannabis aborted the migraine. Lucky us!

[Curtis]

22. I have suffered migraines my entire life

So this is great news to say the least!

<sarcasm>However, I find it impossible that a team of British and Canadian researchers discovered this. I mean they have socialized medicine and our media keeps telling us that socialized medicine cannot develop breakthrus like this <\sarcasm>

[unblock]

23. i find it hard to believe that it all comes down to ONE gene

given how many different types of "migraine" headaches there are, and how different people respond differently to different meds, i find it far more plausible that there are at least a handful of genes involved.

still, handle they can get would be most welcome. i get easily 20+ migraines a month, and have gone entire seasons with a migraine every day. fortunately zomig often helps, and there's always stadol if two zomigs do nothing. i've tried every preventative under the sun and nothing seems to work for more than a month or two, my body always adjusts to it and it's back to the usual migraine routine.

[demigoddess]

24. I'm sorry but I don't think this is the whole answer.

My migraines seemed to start with the birth of my first child after a spinal anesthesia. Then I had some after the birth of my second child. I have always had headaches from chemicals and pregnancy especially if they intersected. Medicines can give me massive migraines that will not be relieved by my usual methods. Perfumes cigarette smoke etc. Sometimes I can go ages without one if I watch processed foods, perfume and stay away from other peoples laundry soap etc. Does not sound genetic to me.

[Duer 157099]

31. Finding the gene involved does not mean that all migraines are caused by a mutation

It's just a baby step in the research process. Once the gene is irrefutably identified (usually by identifying several family members that have the same mutation and the same pathology), then the protein that is derived from the gene can be studied to see why it does what it does and what it means when it doesn't work properly. The people discussed in the article have an apparently rare form of the gene, but all that did was to put a huge arrow in front of the scientists and said "LOOK HERE" at the protein (a potassium-ion channel) that they can now study. THey can see which drugs influence that protein, which other genetic factors influence that protein and so on. It's just a starting point, and a good one.

[Dappleganger]

32. I have mitral valve prolapse and get aura migraines

when not on a beta blocker to control the palpitations. We found out the added benefit when I went on heart meds at the age of 19.

[Duer 157099]

33. Interesting connection

I also have MVP and get aura migraines, and both of those conditions affect women preferentially.

I wonder what the connection is? Hmmmm, interesting.

[Dappleganger]

34. I haven't studied it, only heard it from various doctors.

My mother's best friend had the same thing, MVP with aura migraines. My migraines began in 5th grade but we didn't know about the MVP until my freshman year in college.