Sodium Channel Research
 

I'm just starting this thread as a place to post things related to the ongoing research showing an association between gene mutations in the Nav1.7, 1.8, and 1.9 sodium channels and neuropathy. The second article below is less technical and quite interesting.


16 May 2014

Third Sodium Channel Implicated in Painful Small-Fiber Neuropathy
Mutations in Nav1.9 render pain neurons hyperexcitable

http://www.painresearchforum.org/new...ber-neuropathy


October 29, 2014

The Role of Sodium Channels in Painful Neuropathies

http://www.neurologyadvisor.com/targ...rticle/380020/

"This emphasizes the importance of the research on Nav1.7, Nav1.8, and most recently Nav1.9. These channels seem to be the ones that are specific to nerve pain. Pharmaceutical companies are actively working on drugs for Nav1.7 and Nav1.8 and will probably begin to include Nav1.9, now that it has also been linked to human pain. Finding drugs that selectively block just these channels could be the holy grail of neuropathic pain treatment."



September 20, 2012

Gain-of-function Nav1.8 mutations in painful neuropathy - Faber

http://www.pnas.org/content/109/47/19444.full



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I have read a bit about this too, the nav 1.9 sounds interesting as how I understand it , it can benefit not just people with the mutation but all sfn sufferers, also suggests it can be disease modifying , I'm still waiting for results of 1.7 and 1.8 genetic testing.

Loulou

I am currently waiting for testing on these sodium channels (appointment scheduled for june 18th). LouLou you have had the test? Is it just a blood draw? And any idea how long the results take?

Interesting article. I have always been curious about the ionic channels, but none of my Dr' s have seemed that interested when I bring it up.
I have an anti body (VGKC) related to the potassium channel----and my main symptom was cramping. This article talks about the burning----which so many people on here have.
Are we getting these neuropathys due to something happening in these channels?? or are we getting these neuropathys anyway and these channels are determining the pain pathway?? sorry if it's confusing----I'm just thinking out loud here

Hi there,

I have had the test, it is just blood drawn, it takes ages to come back, months and months. Had mine done in November - still waiting, I have had the potassium channel one too, still haven't had that back either.

My neurologist said they are finding more and more of these genetic mutations related to SFN which will then bring the idiopathic percentage down.

LouLou

I'm happy to hear some people are doing testing for this, and will be anxious to hear results. Were the tests ordered by PCPs or neuros?

In looking into what, if any, supplements might support sodium channel function, I came across a reference to vinpocetine. It's been mentioned on this forum only three times I think, but am wondering if anyone still here has tried it.

HI there,

here in the UK it would have to be ordered by the consultant neurologist, I am surprised there is not a lot of mention about it on this site. as from how I understand it from my nuero that the number of idiopathic cases are going down and will continue to go down now they are discovering these mutations.

What is the test called? I may have missed that.

It's a genetic test. I don't know how specific the tests are that people are getting, but the associated genes are SCN9A, SCN10A, SCN11A. Maybe the full genes are being sequenced.

There is some information about vinpocetine here:

http://www.drugs.com/npp/vinpocetine.html

How do you get those tests done? My neurologist doesn't do it.
I am also very interested in sodium channel research mostly because of how a ketogenic diet can work for epilepsy due to mutations.

The test has to be done by a lab specializing in DNA testing, and I assume would require a doctor's order, although a lot of labs are doing direct to consume testing now. A blood draw is required, so you have to go to Quest or some place like to start the process.

Here's one lab that offers SCN9A sequencing, but SCN10A and SCN11A aren't part of it.

https://www.genedx.com/test-catalog/...thy-sfn/34209/

I think the way this works, and maybe someone else can chime in, is that once certain gene mutations are conclusively identified for a disorder, these test companies will offer targeted screening tests for that disorder.

For example, this Genedx company offers a hereditary neuropathy panel that looks for Charcot-Marie-Tooth and other forms of known inherited neuropathy.

https://www.genedx.com/test-catalog/...thy-sfn/39532/

The cost of these tests can be high, though. They're not mentioning prices on these tests, but somewhere else I saw a neuropathy panel for $1600 but it also didn't included all the latest genes mutations referenced in the latest research.


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My father has been diagnosed with Huntington's disease which is a pretty serious disorder. His diagnosis is clinical. Insurance refuses to pay for the genetic test to help confirm the diagnosis and is additionally rejecting the drug that his neurologist prescribed to help with his chorea because it is expensive. His insurance company is disgraceful, in my opinion. He needs that genetic conformation before the insurance company will even consider that drug, which they might still deny if it gets to that stage.

So, I would guess that insurance would not cover the costs of those tests, if you could even find a neurologist to order it. Especially if there are no different drugs that on the market that have an indication for this, then the treatment path would be the same - gabapentin, Lycra, Cymbalta etc.

His insurance company is indeed disgraceful. Do they think there's another cheaper drug that he should take instead?

With my $5500 insurance deductible, whether insurance would cover it or not, I'd essentially have to pay for it anyway. I'm not sure I'd be inclined to go that route unless there were something that could be done about it, and we're many years away from any targeted drugs on those three sodium channels.

Like I'm doing with my "pre-pre-diabetes" status, I'm just going to assume it's part of the problem and do whatever I possibly can for it. Right now if someone were to force me to take a guess at what's causing my problems, I'd have to say it's mildly elevated sugar levels working in concert with bad genes that are starting to express themselves as I age. Something has me feeling better than I was a year ago, and I have to believe the ALA and LCHF diet are involved.

I'm not sure if there is another drug. I'm still learning about this disease. He is getting one month of it for free somehow, probably as a trial. The drug costs $7000/month. Then I think it will become an insurance struggle to get it covered after that.

I also selfishly want him to get the genetic test because it impacts my life. Children have 50% chance of inheriting this condition and often times will undergo genetic screening because it is such a devastating diagnosis. And I'm sure it will be a battle with my insurance to cover part of this....especially if his diagnosis is just clinical.

There is so much literature on ketogenic diets and epilepsy. It's interesting that you mention this because I just bought a book for my kindle where someone basically complied all the ketogenic research. It only cost $1, so I figured even it was poorly done that it wouldn't that financially disappointing.

http://www.amazon.com/Principia-Keto...owViewpoints=0

Here's a sodium channel drug undergoing clinical trials for treating post-herpetic neuralgia (lingering nerve pain from shingles) and osteoarthritis. Interestingly, it's applied topically. It's only in Phase 2b, however, so it's still years away from possible approval. The ointment is currently being called "TV-45070."

Las Vegas, NV – Monday, April 13, 2015 – (Techsonian) – Teva Pharmaceutical Industries Ltd (ADR) (NYSE:TEVA) and Xenon Pharmaceuticals Inc.

(Nasdaq:XENE) recently proclaimed that the first patient has been enrolled into the Phase 2b study designed to evaluate the safety and efficacy of the novel topically applied TV-45070, (4% and 8% w/w ointment) in patients with postherpetic neuralgia (PHN). TV-45070 is a small molecule inhibitor of the sodium channel Nav1.7 and other sodium channels, including those that are expressed in the pain-sensing peripheral nervous system. It is being developed for the treatment of patients with various pain indications, including neuropathic and osteoarthritis pain.

More info:

http://www.xenon-pharma.com/product-...ain/pain-teva/

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Thanks for the link! I work on clinical trials so I enjoy reading about this type of stuff. There is probably less than a 1 in 5 chance anything makes it to Phase III. It's nice to see companies work on orphan drugs for a change.

I wonder if these tests a reliable, because some private labs are there to earn profit.

HI there,

Convergence Pharmaceuticals are preparing for phase 3 clinic trials for nav 1.7 blocker. They are in preparations for other candidates too, which I believe the next is diabetic neuropathy.

Hi madisongrrl

I am sorry to read about your father's diagnosis. If it is confirmed by genetic testing, you might find the information in this link helpful:

http://www.mayoclinic.org/diseases-c...n/con-20030685

All the best.

Another sodium channel blocker being developed for PN pain is NKTR-171. I've had my eye on it for two years and it's just now in Phase I.

http://www.nektar.com/product_pipeli..._nktr-171.html

Test methodology and validation information is listed in the link.

Thanks. The drug heading into Phase 3 is CNV1014802.

http://www.convergencepharma.com/index.asp?page_id=14

Others in the pipeline:

http://www.convergencepharma.com/index.asp?page_id=16

Convergence was also bought by Biogen earlier this year, so they have deep pockets behind them now.