VGSDs: a potential breakthrough on the horizon for neuropathy pain?

Posted by Hank @jesfactsmon, Jun 22, 2020

Hi, I started this discussion to talk about hope for a cure for neuropathy pain. Soon after my wife developed peripheral neuropathy from chemo in 2014 I found out some information that I was very interested in and excited about at that time and, having followed the progress since then, still am even now. It involves a new non-addictive drug therapy for PN pain which is currently in development that has no opioid like side effects.

Some of you may already have read something about this. For me it started when I read an article online which talked about a toxin from a fish know as the pufferfish called tetrodotoxin (TTX). The pufferfish is a delicacy in restaurants in Japan and has to have the toxin removed by an expert or it could kill the restaurant patron. I found out that TTX may hold the key to solving neuropathic pain. I read as much as I could find back in 2014 and 2015 about this substance. There is a company named Wex Pharmaceuticals which was developing a PN drug back then based on TTX. It was in phase III trials as a potentially life altering solution for PN sufferers. I was so excited I wanted to know what its chances were, and I actually managed to contact a representative from Wex who told me back then that the chances of there being an actual drug on the market as a result of these trials was iffy at best and possibly years away. Later I found out that a drug name selected for it back then was Tectin.

Having heard from the horse's mouth (so to speak) that this thing was not likely to happen soon I quit thinking about it until a few months ago when I happened upon an article online by The Scientist magazine. It contained some info I did not know before as to what TTX actually does to relieve pain. I found out that TTX is what is known as a "voltage gated sodium channel" (VGSD) blocker. The picture I included (hopefully it shows up) is of several VGSDs (in purple) along a neuron.

As I understand it, VGSDs are channels located on the surface of nociceptors (pain neurons) through which nociceptors get their pain responses triggered. In humans there are 9 different VGSDs and the one that has a direct relationship with PN pain is called NaV1.7 which is generated by the SCN9A gene. There are a variety of substances that effectively block NaV1.7, which stops the pain of PN. One of the best of these is cocaine. Unfortunately, things like cocaine don't just block NaV1.7 but they block some of the other 8 VGSD's as well and that is not good. Because the other VGSD's are responsible for other functions in the body which you would not want to stop, like heart function, etc. Now after Wex pharmaceuticals were in phase III trials with Tectin they did not have good luck with it apparently and they shut down that trial. However I have found out that Wex has another ongoing trial with a followup effort called Halneuron. That drug has recently been in phase II trials for cancer related pain such as chemo induced peripheral neuropathy.

Now Halneuron may or may not eventually become a viable FDA approved drug treatment. But I believe from what I have read that there is a significant scientific research effort ongoing by various companies to find something to block the NaV1.7 VGSD and not block the other 8 VGSD's at the same time, thus causing relief from pain for PN sufferers without jeopardizing their health in other ways. A company called Chromocell is also researching a drug (named simply CC8464) based on VGSDs and was entering phase II trials with it as of September 2019. There may be other companies working on VGSD blockers as well.

The article which I mentioned earlier from The Scientist is from 2017 and explains really clearly how the NaV1.7 VGSD functions and what has been done to determine how this might eventually develop into a breakthrough solution for PN. Here is the link to that article for those interested:
https://www.the-scientist.com/features/targeting-sodium-channels-for-pain-relief-30147
Just wanted to tell you guys about this so you are aware of this avenue of hope. It's nice to know somebody is working on SOMETHING that might help people with this ridiculous affliction of PN! VGSD research has been ongoing for many years (at least since 2006) and I have personally been waiting for it to develop into a useful drug for 6 years. I have not heard anything more recent that Sept. 2019 about the current status of any of these drug trials but do hope for some good news before too long.

And finally, if anyone reading this knows anything further that they can add about this research or these drug trials, please let me know. I'd be very interested. Thanks, Hank

Interested in more discussions like this? Go to the Neuropathy Support Group.

Thank you for your response...sometimes not dismissing is as important as having an answer. The symptoms that bother me the most are numbness in feet that certainly informs how I walk, and absolutely everything about feeling secure when standing. Also tingling and I guess what most people might describe as pain but I think of it as restless legs (mostly in feet and ankles). I am so worried about winding up in a wheelchair and having limited mobility. This all started with swollen feet, ankles and calves. I went to my PCP who sent me off for ultrasounds to rule out clots which I didn't have. She never followed up with me so I went to a podiatrist who did a couple of routine tests and declared it neuropathy. But she had no answer as to why. So I started my own research and went back to PCP to no avail. And so the saga begins!

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All of the neuropathy symptoms bother me. The burning, coldness, numbness, buzzing of the toes, feet, calves
and the effect on my quality of life (difficult to stand, sit, walk exercise). And knowing that THERE IS NO CURE! That causes me to suffer from anxiety and depression.

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I am so fed up with these doctors with no answers! Neuropathy is a nerve issue. Why do they have Zero information for us? I think they just don't care because it's not important to them which makes no Sense because there is money to be made from helping us. I am like some of you here who has no reason for neuropathy that just came on suddenly out of nowhere. I went to see a Neurologist who told me I was pre diabetic as though that were an answer, it isn't. My AIC is 5.7. Nomal range is below 5.6 so I am one single digit off and diabetic neuropathy doesn't start for diabetics until they hit about 6.7. I had chemo 13 years ago. Neuropathy from Chemo doesn't take 13 years and also usually goes away.
The numbness in my feet started a few months ago and Spread FAST and is driving me crazy!
I can't say there is no reason for it because of course there is but no one knows what it is. The neurologist did some blood work but never bothered to call me with the results. They just throw their hands up in the air.

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@johnbishop

Hank, my big hope for future patients is a method, treatment or therapy that reverses nerve damage instead of just treating the symptoms which to me is better. Just my humble opinion and hope for all you pain warriors 🙂

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I whole heartily agree!

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Hi my son is about 1year 5 months diagnosed with choroid plexus carcinoma. Did removal surgery at 2 months old and started chemotherapy treatment at 12 months old, he finished two circles already and our health provider says he is not going to receive a treatment anymore because it is not working. According to CT scan the tumor has doubled or spread that's the reason why. Now they don't have a plan about my son's condition and he keeps on vomiting a lot, doesn't eat nothing.

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